Despite all efforts to treat hypertension, it is still responsible for 10.8 million deaths annually. The aim of this study was to compare the effects of continuous moderate-intensity training, strength training combined with continuous moderate-intensity training and strength training combined with high-intensity interval training in adults with high blood pressure.

A 12-week randomized control trial was performed. A total of 100 volunteers, 51 women and 49 men with hypertension participated. The sample was randomly assigned into three intervention groups and one control group.

All intervention groups significantly improved their hemodynamic parameters, body composition, lipid profile, glucose, and physical fitness as compared to the control group. Both combined training groups showed greater improvements than the moderate-intensity continuous training group. However, the strength group combined with the moderate-intensity continuous group showed the greatest benefits in systolic, diastolic and mean arterial pressure, of -13.4 mmHg, -6.8 mmHg and -8.9 mmHg respectively, abdominal circumference, upper and lower limb strength and VO₂peak, versus the continuous moderate-intensity group; it also achieved greater reductions in systolic and mean blood pressure, up to -6.8 mmHg and 4.3 mmHg respectively, than the strength group combined with the high intensity interval group.

Performing a strength training program combined with continuous moderate intensity training, 2 days per week for 12 weeks, produces significant improvements in cardiometabolic biomarkers, body composition, and physical condition of adults with hypertension, with these adaptations being superior to those produced by continuous moderate-intensity training and strength training combined with high-intensity intervallic training.

Flow-diverter stents are a potent and efficient tool in the instrumentarium of neurointerventional radiologists for the treatment of intracranial aneurysms. With their implementation, some adverse effects and complications such as hemorrhagic and ischemic ones, have been seen as a potential downfall of the method. In-stent stenosis is one such complication, which until now has not received enormous attention due to its seemingly benign characteristic. In our study we propose a different point of view on this matter and aim to establish a potential mechanism for its development: a subacute postprocedural stent deformation, due to segmental vessel constriction as a reaction to the implant.

We enrolled 48 patients between the ages of 31 and 71 (8 men) with aneurysms on the distal portions of the ICA, all of whom were treated with the p64 flow-diverter stent, to assess the incidence of this phenomenon, as well as establish a correlation between it and subsequent clinical symptoms. A protocol for short-term follow-up, consisting only of a high-dose fluoroscopy image of the implant (conducted on the 14th postprocedural day) was implemented to assess the state of the implant before endothelization was to be expected.

Stent deformities were seen in 58% of cases. One patient with an observed stent deformity presented with several episodes of acute contralateral 1-sided weakness of the limbs. Seventy-one percent of those patients presented with a mild/moderate unilateral headache postprocedurally. A correlation between the deformity and a subsequent narrowing of the parent vessel diameter was established on follow-ups. Notable in-stent stenosis was reported in 35% of all cases.

Cases with subacute stent deformities are presented in a nonnegligible percent of flow-diversion therapies with the p64 stent. A statistically significant association between the observed deformation and subsequent in-stent stenosis was observed on follow-up.

Oxidative stress plays an important role in the development of hypertension (HTN). A population-based cross-sectional study was conducted in Fujian province of China. The construction of FoodL-OBS relied on diet and lifestyle components, which included four food and six lifestyle factors. Multivariable-adjusted logistic regression was performed to investigate the association between FoodL-OBS and the risk of HTN. A subgroup analysis was also conducted. Restricted cubic spline (RCS) regression was used to elucidate the dose-response relationship between FoodL-OBS and the risk of HTN. A total of 9578 participants were included, 3271 of whom suffered from HTN. The results of multivariable logistic regression analysis showed that the HTN risk decreased by 14% for each FoodL-OBS unit added [OR: 0.86 (0.84, 0.88), p < 0.01]. Compared with participants with the lowest levels of Food-L-OBS, those with the highest quartile were less likely to have HTN [0.43 (0.37, 0.50)]. Further stratified analysis showed that Food-L-OBS was negatively associated with the risk of HTN, which was statistically significant in participants in subgroups of ≤60 years, female, and no-dyslipidemia. The results of RCS showed a linear negative correlation between Food-L-OBS and HTN in men, but not in women. In conclusion, FoodL-OBS was negatively associated with HTN, and a healthy lifestyle and antioxidant-rich diet may be useful for preventing HTN.

Systemic aging influences various physiological processes and contributes to structural and functional decline in cardiac tissue. These alterations include an increased incidence of left ventricular hypertrophy, a decline in left ventricular diastolic function, left atrial dilation, atrial fibrillation, myocardial fibrosis and cardiac amyloidosis, elevating susceptibility to chronic heart failure (HF) in the elderly. Age-related cardiac dysfunction stems from prolonged exposure to genomic, epigenetic, oxidative, autophagic, inflammatory and regenerative stresses, along with the accumulation of senescent cells. Concurrently, age-related structural and functional changes in the vascular system, attributed to endothelial dysfunction, arterial stiffness, impaired angiogenesis, oxidative stress and inflammation, impose additional strain on the heart. Dysregulated mechanosignalling and impaired nitric oxide signalling play critical roles in the age-related vascular dysfunction associated with HF. Metabolic aging drives intricate shifts in glucose and lipid metabolism, leading to insulin resistance, mitochondrial dysfunction and lipid accumulation within cardiomyocytes. These alterations contribute to cardiac hypertrophy, fibrosis and impaired contractility, ultimately propelling HF. Systemic low-grade chronic inflammation, in conjunction with the senescence-associated secretory phenotype, aggravates cardiac dysfunction with age by promoting immune cell infiltration into the myocardium, fostering HF. This is further exacerbated by age-related comorbidities like coronary artery disease (CAD), atherosclerosis, hypertension, obesity, diabetes and chronic kidney disease (CKD). CAD and atherosclerosis induce myocardial ischaemia and adverse remodelling, while hypertension contributes to cardiac hypertrophy and fibrosis. Obesity-associated insulin resistance, inflammation and dyslipidaemia create a profibrotic cardiac environment, whereas diabetes-related metabolic disturbances further impair cardiac function. CKD-related fluid overload, electrolyte imbalances and uraemic toxins exacerbate HF through systemic inflammation and neurohormonal renin-angiotensin-aldosterone system (RAAS) activation. Recognizing aging as a modifiable process has opened avenues to target systemic aging in HF through both lifestyle interventions and therapeutics. Exercise, known for its antioxidant effects, can partly reverse pathological cardiac remodelling in the elderly by countering processes linked to age-related chronic HF, such as mitochondrial dysfunction, inflammation, senescence and declining cardiomyocyte regeneration. Dietary interventions such as plant-based and ketogenic diets, caloric restriction and macronutrient supplementation are instrumental in maintaining energy balance, reducing adiposity and addressing micronutrient and macronutrient imbalances associated with age-related HF. Therapeutic advancements targeting systemic aging in HF are underway. Key approaches include senomorphics and senolytics to limit senescence, antioxidants targeting mitochondrial stress, anti-inflammatory drugs like interleukin (IL)-1β inhibitors, metabolic rejuvenators such as nicotinamide riboside, resveratrol and sirtuin (SIRT) activators and autophagy enhancers like metformin and sodium-glucose cotransporter 2 (SGLT2) inhibitors, all of which offer potential for preserving cardiac function and alleviating the age-related HF burden.

Sex-specific differences in OSA-associated symptoms and polysomnographic findings are well recognized. However, sex differences in intermediate pathways potentially linking OSA and cardiometabolic outcomes are limited. OSA is known to be associated with decreased nitric oxide (NO)-related vasodilation and endothelial dysfunction. The current study sought to characterize the independent association between OSA severity and overnight NO metabolites (i.e. markers of oxidative stress) and determine if there were differences by sex in persons with type 2 diabetes mellitus (T2DM).

Adults with T2DM and undiagnosed OSA were recruited from the community. Demographic information, an overnight polysomnogram, and pre- and post-sleep plasma samples were collected. The association between OSA and nitrite and nitrate levels were examined using multivariable linear regression. Analyses were done for the entire sample and stratified by sex.

The sample included 83 participants with 52 % men. Stratified, fully adjusted models showed that compared to women with mild OSA, women with moderate or severe OSA did not exhibit the expected decline in overnight nitrate levels: 4.84 μM (-12.3, 2.7: p = 0.09) and 5.82 μM (-4.7, 16.3: p < 0.01) for moderate and severe OSA, respectively. Overnight nitrate levels decreased in males regardless of OSA severity, without significant differences across severity categories. An interaction between OSA severity and sex was seen for post-sleep nitrates in women with severe OSA.

The association between OSA and overnight nitrates varies by sex and OSA severity. Women with severe OSA did not have a decline in overnight nitrate levels whereas men did, suggesting they have higher overnight oxidative stress.

Poor blood pressure control in treated patients with hypertension is an important topic in the field of hypertension, and an unmet need for new therapeutic drugs remains. Soluble guanylate cyclase (sGC), a key signal transduction enzyme responsible for vasodilation, has attracted increasing interest as a therapeutic target in various cardiovascular diseases. Two different sGC agonists, sGC stimulators and activators, can increase its enzymatic activity in reduced and oxidized/apo forms, respectively. With some sGC agonists being already in clinical use, drugs in this category are expected to become new therapeutic agents for various conditions, including hypertension. In this review, we summarize the current knowledge on the antihypertensive effects of sGC agonists in various preclinical studies involving animal models of spontaneous hypertension, salt-sensitive hypertension, nitric oxide-deficient hypertension, renin-angiotensin-aldosterone system-dependent hypertension, malignant hypertension, metabolic syndrome, renoprival hypertension, renovascular hypertension, drug-induced hypertension, pregnancy hypertension, and treatment-resistant hypertension. Our compilation provides a comprehensive rationale for advancing the clinical development of sGC agonists for the treatment of hypertension.

Erectile dysfunction (ED) is a prevalent condition affecting male sexual health, characterized by the inability to achieve or maintain satisfactory erections. ED has a multifactorial pathogenesis in which psychological, hormonal, neurologic, cardiovascular, and lifestyle factors all contribute to a progressive decline of erectile function. A critical underlying mechanism involves oxidative stress (OS), an imbalance between reactive oxygen species (ROS) production and antioxidant defenses, which disrupts endothelial function, reduces nitric oxide (NO) bioavailability, and contributes to vascular dysfunction. This narrative review explores the interplay between OS and ED, focusing on the roles of ROS sources such as NADPH oxidase, xanthine oxidase, uncoupled nitric oxide synthase, and mitochondrial dysfunction. It examines the impact of OS on chronic conditions like hypertension, diabetes mellitus, hyperlipidemia, hypogonadism, and lifestyle factors like smoking and obesity, which exacerbate ED through endothelial and systemic effects. Emerging research underscores the potential of antioxidant therapies and lifestyle interventions to restore redox balance, improve endothelial function, and mitigate ED's progression. This review also highlights gaps in understanding the molecular pathways linking ROS to ED, emphasizing the need for further research to develop targeted therapeutic strategies.

Peripheral artery disease (PAD) is a major public health concern due to its high prevalence, severe impact on individuals' health and quality of life, and substantial economic burden. Pharmacological interventions are still limited with numbers needed-to-treat ranging from 6 (cilostazol) to 50 (aspirin, statins, and vorapaxar).

This randomized, placebo-controlled, double-blinded crossover interventional trial aims to measure the effect of L-citrulline and tetrahydrobiopterin (H4Bip) on walking distance in patients with PAD, stratified by plasma levels of asymmetric dimethyl L-arginine (ADMA), the endogenous inhibitor of endothelial nitric oxide (NO) synthase.

We measured preinterventional ADMA levels in 51 patients with PAD in Australia and Germany with mean changes in absolute claudication distance (dACD) as the primary outcome upon orally supplementing the L-arginine precursor, L-citrulline (3 g) twice daily for 12 weeks, and, in one arm, additionally H4Bip (0.45 g) once per day for a further 2 weeks.

Preinterventional ADMA levels were pathological (>0.4 μM) in 34 patients. Supplementation with L-citrulline significantly increased the mean plasma levels of both L-citrulline and L-arginine, from 41.8 ± 2.7 μmol/l to 246.3 ± 67.3 μmol/l (P = 0.004) and from 75.2 ± 4.2 μmol/l to 119.2 ± 6.9 μmol/l (P < 0.0001) respectively, when compared with placebo. dACD in % of control was significantly improved by L-citrulline vs placebo (20.11% ± 4.50% vs 5.73% ± 2.74%, respectively; P = 0.011). Further addition of H4Bip increased the mean percentage dACD to 28.15% ± 6.84% (P = 0.021), but only in patients with preinterventional pathological ADMA levels.

L-citrulline and, when ADMA levels are pathological, H4Bip are effective nutritional interventions in patients with PAD warranting further confirmatory trials.

The carotid body (CB), the main peripheral arterial chemoreceptor, exhibits considerable structural and neurochemical plasticity in response to pathological conditions such as high blood pressure. Previous studies have shown that morphological alterations in the hypertensive CB are characterized by enlarged parenchyma due to cellular hypertrophy and hyperplasia, and vasodilation. To test whether hypertension can also induce neoangiogenesis and modulate its chemosensory function, we examined the immunohistochemical expression of two angiogenic factors, vascular endothelial growth factor (VEGF) and endothelin-1 (ET), and their corresponding receptors in the CB of adult spontaneously hypertensive rats (SHRs), and compared their expression patterns to that of age-matched normotensive Wistar rats (NWR). We found an increased VEGF-A and B, and VEGFR-2 expression in glomus and endothelial cells in the enlarged CB glomeruli of SHRs compared with that in NWR. Conversely, weaker immunoreactivity to VEGFR-1 was detected in cell clusters of the hypertensive CB. The expression of endothelin-converting enzyme 1 and its receptor ETA was higher in a subset of glomus cells in the normotensive CB, while the immunoreactivity to the ETB receptor was enhanced in endothelial cells of CB blood vessels in SHRs. The elevated endothelial expression of VEGF and ET-1 suggests their role as local vascular remodeling factors in the adaptation to hypertension, though their involvement in the cellular rearrangement and modulation of chemosensory function could also be implied.

Cardioplegic arrest and cardiopulmonary bypass (CP/CPB) are known to engender microvascular dysfunction in patients undergoing cardiac surgery. These effects are significantly varied by patient comorbidities including diabetes and hypertension. Both diabetes and hypertension are associated with worse outcomes after cardiac surgery, partly related to increased microvascular complications. In this review, we examine several key facets of microvascular dysfunction after CP/CPB: microvascular endothelial and vasomotor dysfunction, altered gene and protein expression, endothelial adherens junction dysfunction, and programmed cell death as they relate to diabetes and hypertension. This review examines both classical techniques, including microvessel reactivity assays, and modern multiomic approaches to characterizing these microvascular changes.

Flavonoids are naturally occurring dietary phytochemicals with significant antioxidant effects aside from several health benefits. People often consume them in combination with other food components. Compiling data establishes a link between bioactive flavonoids and prevention of several diseases in animal models, including cardiovascular diseases, diabetes, gut dysbiosis, and metabolic dysfunction-associated steatotic liver disease (MASLD). However, numerous clinical studies have demonstrated the ineffectiveness of flavonoids contradicting rodent models, thereby challenging the validity of using flavonoids as dietary supplements.

This review provides a clinical perspective to emphasize the effective roles of dietary flavonoids as well as to summarize their specific mechanisms in animals briefly.

First, this review offers an in-depth elucidation of the metabolic processes of flavonoids within human, encompassing the small, large intestine, and the liver. Furthermore, the review provides a comprehensive overview of the various functions of flavonoids in the gastrointestinal tract, including hindering the breakdown and assimilation of macronutrients, such as polysaccharides and lipids, regulating gut hormone secretion as well as inhibition of mineral iron absorption. In the large intestine, an unabsorbed major portion of flavonoids interact with the gut flora leading to their biotransformation. Once absorbed and circulated in the bloodstream, bioactive flavonoids or their metabolites exert numerous beneficial systemic effects. Lastly, we examine the protective effects of flavonoids in several metabolic disorders, including endothelial dysfunction, MASLD, cardiovascular disease, obesity, hyperlipidemia, and insulin resistance. In conclusion, this review outlines the safety and future prospects of flavonoids in the field of health, especially in the prevention of metabolic syndrome (MetS).

In the past decade, flow diverters (FDs) have increasingly been used to treat cerebral aneurysms with unfavorable morphology in which other endovascular techniques fall short of being as effective. In-stent stenosis (ISS) is one of the most puzzling and frequent risks of flow diversion therapy observed on follow-ups. This complication, although mostly placid in its clinical course, can have dire consequences if patients become symptomatic. ISS is associated with many factors, none of which have been demonstrated to date to be solely responsible for the phenomenon.

This study was aimed at evaluating ISS incidence in patients in our clinic who were treated with flow-diverters for aneurysms, located on the supraclinoid segments of the internal carotid artery between September 2022 and May 2023. A retrospective analysis was conducted, which included 137 patients with a total of 142 aneurysms being treated. The main hypothesis was that oversizing of the implant might play a role in ISS development. The performed statistical analysis, aimed at finding a correlation between it and vessel lumen narrowing on the follow-ups. The effects of other known risk factors, such as sex, age, smoking, and hypertension, were also analyzed.

Stent oversizing with respect to the parent artery was positively correlated with subsequent ISS occurrence and severity. Older age was a protective factor against ISS. Patients who actively smoked had diminished risk of developing severe ISS.

Stent oversizing can lead to ISS development, which might be more pronounced with larger implant-to-vessel sizing discrepancies. To achieve optimal results, the choice of implant diameter should consider all segments of the vessel in which it will be implanted. In cases of severe symptomatic ISS, continuation of dual anti-platelet therapy is a reasonable and effective option to address this complication.

Sleep apnea involves almost one billion individuals throughout the world, including 40 million Americans. Of major medical concern is the fact that the prevalence of sleep apnea is significantly increasing due to the epidemic of obesity, physical inactivity, and diabetes mellitus which are important risk factors for the development and persistence of sleep apnea in individuals. Sleep apnea is characterized by multiple episodes of apnea or hypopnea during sleep, which cause nocturnal arousals, gasping for breath during the night, daytime sleepiness, irritability, forgetfulness, fatigue and recurrent headaches. Obstructive sleep apnea occurs when upper airway obstruction occurs in an individual during sleep with absent or markedly reduced airflow in the presence of continued activity of inspiratory thoracic and diaphragmatic muscles. Central sleep apnea is defined as the absence or the significant reduction of naso-oral airflow due to the withdrawal during sleep of ponto-medullary respiratory center stimulation of the nerves of the inspiratory thoracic and diaphragmatic muscles and absence of contraction of these muscles during apnea. Complex sleep apnea occurs when an individual exhibits characteristics of both obstructive and central sleep apnea. The severity of sleep apnea is measured by polysomnography and the apnea hypopnea index (AHI), which is the average number of apneas and hypopneas per hour of sleep measured by polysomnography. Sleep apnea is mild if the AHI is 5-14/h with no or mild symptoms, moderate if the AHI is 15 to 30/h with occasional daytime sleepiness, and severe if the AHI is >30/h with frequent daytime sleepiness that interferes with the normal activities of daily life. Chronic sleep apneas and hypopneas followed by compensatory hyperpneas are associated with significant adverse cardiovascular consequences including: 1) recurrent hypoxemia and hypercarbia; 2) Increased sympathetic nerve activity and decreased parasympathetic nerve activity; 3) oxidative stress and vascular endothelial dysfunction; and 4) cardiac remodeling and cardiovascular disease. Moderate or severe sleep apnea significantly increases the risk of coronary artery disease, congestive heart failure, cerebral vascular events (strokes), and cardiac dysrhythmias, and also increase the morbidity and mortality of these diseases. Nevertheless, sleep apnea is currently underdiagnosed and untreated in many individuals due to the challenges in the prediction and detection of sleep apnea and a lack of well-defined optimal treatment guidelines. Chronic continuous positive airway pressure for ≥4 h/night for >70% of nights is beneficial in the treatment of patients with sleep apnea. CPAP Improves sleep quality, reduces the AHI, augments cardiac output and increases oxygen delivery to brain and heart, reduces resistant hypertension, decreases cardiac dysrhythmias, and reduces daytime sleepiness. The present article discusses the diagnosis of obstructive sleep apnea, central sleep apnea, and complex apnea. Thereafter the important pathophysiologic mechanisms in sleep apnea and the relationship of these pathophysiologic mechanics to atherosclerotic vascular disease are reviewed. Guidelines are then provided for the treatment of mild, moderate and severe sleep apnea. In order to reduce the cardiovascular morbidity and mortality caused by sleep apnea and facilitate the diagnosis and the long-term, effective treatment of sleep apnea in patients, the close cooperation is necessary of cardiovascular specialists, pulmonary specialists, and respiratory therapy/rehabilitation specialists.

Hypertension, a prevalent cardiovascular condition globally, remains a significant public health concern due to its association with increased cardiovascular morbidity and mortality. Despite the availability of various antihypertensive therapies, achieving optimal blood pressure control in patients remains a challenge. Valsartan/sacubitril (ARNi), marketed as Entresto by Novartis, combines valsartan, an angiotensin receptor blocker, with sacubitril, an inhibitor of neprilysin. Neprilysin is responsible for breaking down natriuretic peptides and other vasoactive substances. Inhibiting neprilysin prevents the degradation of natriuretic peptides, enhancing their beneficial effects on blood pressure regulation. Natriuretic Peptides, including atrial natriuretic peptide (ANP) and brain natriuretic peptides (BNP), play pivotal roles in regulating blood pressure and cardiovascular homeostasis by promoting vasodilation, natriuresis, and antagonizing the renin-angiotensin-aldosterone system. Therefore, this combo drug lessens sensitivity to natriuretic peptides and tackles the processes in hypertension that activate the renin-angiotensin-aldosterone system. This review provides an overview of how natriuretic peptides (NPs) contribute to blood pressure regulation for the treatment of hypertension through inhibiting neprilysin. It highlights the ARNi's dual action that works synergistically by blocking the harmful effects of angiotensin II on blood vessels while simultaneously increasing the levels of beneficial natriuretic peptides. Schematic representation of the mechanism of action of ARNi. Abbreviation: -Renin angiotensin aldosterone system (RAAS), Natriuretic peptides (NP), Atrial Natriuretic peptide (ANP), Brain natriuretic peptide (BNP), C-type natriuretic peptide (CNP), Angiotensin II (Ang II), Angiotensin receptor neprilysin inhibitor (ARNI).

This comprehensive review explores the biological functions of Perilla frutescens seed proteins and peptides, highlighting their significant potential for health and therapeutic applications. This review delves into the mechanisms through which perilla peptides combat oxidative stress and protect cells from oxidative damage, encompassing free radical scavenging, metal chelating, in vivo antioxidant, and cytoprotective activities. Perilla peptides exhibit robust anti-aging properties by activating the Nrf2 pathway, enhancing cellular antioxidant capacity, and supporting skin health through the promotion of keratinocyte growth, maintenance of collagen integrity, and reduction in senescent cells. Additionally, they demonstrate antidiabetic activity by inhibiting α-amylase and α-glucosidase. The cardioprotective effects of perilla peptides are underscored by ACE-inhibitory activities and combat oxidative stress through enhanced antioxidant defenses. Further, perilla peptides contribute to improved gut health by enhancing beneficial gut flora and reinforcing intestinal barriers. In liver, kidney, and testicular health, they reduce oxidative stress and apoptotic damage while normalizing electrolyte levels and protecting against cyclophosphamide-induced reproductive and endocrine disruptions by restoring hormone synthesis. Promising anticancer potential is also demonstrated by perilla peptides through the inhibition of key cancer cell lines, alongside their anti-inflammatory and immunomodulating activities. Their anti-fatigue effects enhance exercise performance and muscle function, while perilla seed peptide nanoparticles show potential for targeted drug delivery. The diverse applications of perilla peptides support their potential as functional food additives and therapeutic agents.

Obstructive sleep apnea (OSA) is often a lifestyle disease associated with obesity, which is rapidly evolving as a major health concern with diverse multisystemic implications. To prevent and mitigate its adverse effects and reduce its burden on society, its aetiopathogeneses must be precisely understood. Numerous studies focusing on the range of diverse anatomic, functional, and lifestyle factors have already been carried out to determine the possible contributory roles of these factors in OSA. Recently, evidence to validate the role of inflammatory pathways and immune mechanisms in the aetiopathogeneses of OSA is being developed. This allows for further research and translation of such knowledge for targeted therapeutic and preventive interventions in patients with or who are at risk of developing OSA.

Betalains are naturally occurring pigments sourced mainly from Beta vulgaris (beetroot), Hylocereus spp. (dragon fruit), Amaranthus spp., and Opuntia spp. Betalains are widely used for their vibrant colors and health-promoting properties. These nitrogenous, water-soluble pigments are crucial colorants in the food industry, responsible for the red, purple, and yellow plant tissues, predominantly in the order Caryophyllales. They are grouped into betacyanins, with reddish-violet hues, and betaxanthins, yellow to orange. Examples include beetroot stems for betacyanins and yellow pitaya pulp for betaxanthins. Several pharmacological activities were reviewed in the scientific literature, describing their potential implications for human health. In this review, we focused on the main and latest studies on the pharmacological effects and mechanisms of betalains, including antioxidant, anti-inflammatory, antihypertensive, hypolipidemic, antidiabetic, hepatoprotective, neuroprotective, anticancer, and antimicrobial properties, in both in vitro and in vivo studies. Overall, betalain consumption is considered safe, with no major adverse effects or allergic reactions reported. We also approached topics such as the pharmacokinetics, bioavailability, stability, and enhanced stabilization of betalains. This article provides a comprehensive overview of bioactive potential of betalains, highlighting the biochemical mechanisms involved. The current knowledge broadens the clinical applicability of betalains, making them potential sources of nutraceutical compounds that can be used to develop functional foods.

Cerebral small vessel disease (cSVD) refers to the age-dependent pathological processes involving the brain small vessels and leading to vascular cognitive impairment, intracerebral hemorrhage, and acute lacunar ischemic stroke. Despite the significant public health burden of cSVD, disease-specific therapeutics remain unavailable due to the incomplete understanding of the underlying pathophysiological mechanisms. Recent advances in neuroimaging acquisition and processing capabilities as well as findings from cSVD animal models have revealed critical roles of several age-dependent processes in cSVD pathogenesis including arterial stiffness, vascular oxidative stress, low-grade systemic inflammation, gut dysbiosis, and increased salt intake. These factors interact to cause a state of endothelial cell dysfunction impairing cerebral blood flow regulation and breaking the blood brain barrier. Neuroinflammation follows resulting in neuronal injury and cSVD clinical manifestations. Impairment of the cerebral waste clearance through the glymphatic system is another potential process that has been recently highlighted contributing to the cognitive decline. This review details these mechanisms and attempts to explain their complex interactions. In addition, the relevant knowledge gaps in cSVD mechanistic understanding are identified and a systematic approach to future translational and early phase clinical research is proposed in order to reveal new cSVD mechanisms and develop disease-specific therapeutics.

Limited literature exists on the vascular reactivity of the radial and ulnar arteries in hypertensive patients following radial artery cannulation. This study assessed the vascular reactivity of the radial and ulnar arteries by comparing Doppler images and laser speckle contrast imaging (LSCI) obtained from both normotensive and hypertensive patients after radial artery cannulation under general anesthesia.

This study recruited 99 normotensive and 99 hypertensive patients who required arterial cannulation under general anesthesia. In the course of research, to evaluate the impact of hypertension on arterial reactivity, we employed duplex Doppler ultrasonography to measure the inner diameter (ID), resistance index (RI) and mean volume flow (MVF) of both arteries at five different time points. We equally performed perfusion of thumb and little finger by laser speckle contrast imaging.

After radial artery cannulation, the hypertensive group showed less increase in radial ID and less decrease in RI compared to the normotensive group. The MVF increase was also less pronounced in hypertensive patients, while both groups demonstrated equivalent ulnar ID changes, and the normotensive group exhibited a more significant decrease in RI and a greater MVF increase. Thumb perfusion decreased post-cannulation in both groups, with the hypertensive group showing a less robust recovery. Little finger perfusion increased after artery cannulation in both groups, but the hypertensive group's increase was lower. The incidence of vasospasm in the hypertensive group is higher than that in the normotensive group.

The radial and ulnar arteries in hypertensive patients may lack a compensatory response to radial artery cannulation during general anesthesia.

Background/Objectives: Increased sodium chloride (NaCl) intake led to leukocyte activation and impaired vasodilatation via increased oxidative stress in human/animal models. Interestingly, subpressor doses of angiotensin II (AngII) restored endothelium-dependent vascular reactivity, which was impaired in a high-salt (HS) diet in animal models. Therefore, the present study aimed to assess the effects of AngII exposure following high salt (HS) loading on endothelial cells' (ECs') viability, activation, and reactive oxygen species (ROS) production. Methods: The fifth passage of human aortic endothelial cells (HAECs) was cultured for 24, 48, and 72 h with NaCl, namely, the control (270 mOsmol/kg), HS320 (320 mOsmol/kg), and HS350 (350 mOsmol/kg). AngII was administered at the half-time of the NaCl incubation (10-4-10-7 mol/L). Results: The cell viability was significantly reduced after 24 h in the HS350 group and in all groups after longer incubation. AngII partly preserved the viability in the HAECs with shorter exposure and lower concentrations of NaCl. Intracellular hydrogen peroxide (H2O2) and peroxynitrite (ONOO-) significantly increased in the HS320 group following AngII exposure compared to the control, while it decreased in the HS350 group compared to the HS control. A significant decrease in superoxide anion (O2.-) formation was observed following AngII exposure at 10-5, 10-6, and 10-7 mol/L for both HS groups. There was a significant decrease in intracellular adhesion molecule 1 (ICAM-1) and endoglin expression in both groups following treatment with 10-4 and 10-5 mol/L of AngII. Conclusions: The results demonstrated that AngII significantly reduced ROS production at HS350 concentrations and modulated the viability, proliferation, and activation states in ECs.

Hypertensive nephropathy (HN) is a leading cause of chronic kidney disease (CKD) and end-stage renal disease (ESRD), contributing to significant morbidity, mortality, and rising healthcare costs. In this review article, we explore the role of epigenetic mechanisms in HN progression and their potential therapeutic implications. We begin by examining key epigenetic modifications-DNA methylation, histone modifications, and non-coding RNAs-observed in kidney disease. Next, we discuss the underlying pathophysiology of HN and highlight current in vitro and in vivo models used to study the condition. Finally, we compare various types of HN-induced renal injury and their associated epigenetic mechanisms with those observed in other kidney injury models, drawing inferences on potential epigenetic therapies for HN. The information gathered in this work indicate that epigenetic mechanisms can drive the progression of HN by regulating key molecular signaling pathways involved in renal damage and fibrosis. The limitations of Renin-Angiotensin-Aldosterone System (RAAS) inhibitors underscore the need for alternative treatments targeting epigenetic pathways. This review emphasizes the importance of further research into the epigenetic regulation of HN to develop more effective therapies and preventive strategies. Identifying novel epigenetic markers could provide new therapeutic opportunities for managing CKD and reducing the burden of ESRD.

Sickle cell disease (SCD) is canonically characterized by reduced red blood cell (RBC) deformability, leading to microvascular obstruction and inflammation. Although the biophysical properties of sickle RBCs are known to influence SCD vasculopathy, the contribution of poor RBC deformability to endothelial dysfunction has yet to be fully explored. Leveraging interrelated in vitro and in silico approaches, we introduce a new paradigm of SCD vasculopathy in which poorly deformable sickle RBCs directly cause endothelial dysfunction via mechanotransduction, during which endothelial cells sense and pathophysiologically respond to aberrant physical forces independently of microvascular obstruction, adhesion, or hemolysis. We demonstrate that perfusion of sickle RBCs or pharmacologically-dehydrated healthy RBCs into small venule-sized "endothelialized" microfluidics leads to pathologic physical interactions with endothelial cells that directly induce inflammatory pathways. Using a combination of computational simulations and large venule-sized endothelialized microfluidics, we observed that perfusion of heterogeneous sickle RBC subpopulations with varying deformability, as well as suspensions of dehydrated normal RBCs admixed with normal RBCs, leads to aberrant margination of the less-deformable RBC subpopulations toward the vessel walls, causing localized, increased shear stress. Increased wall stress is dependent on the degree of subpopulation heterogeneity and oxygen tension and leads to inflammatory endothelial gene expression via mechanotransductive pathways. Our multifaceted approach demonstrates that the presence of sickle RBCs with reduced deformability leads directly to pathological physical (ie, direct collisions and/or compressive forces) and shear-mediated interactions with endothelial cells and induces an inflammatory response, thereby elucidating the ubiquity of vascular dysfunction in SCD.

Cardiovascular diseases (CVDs) are a major cause of death in patients undergoing hemodialysis (HD). Blood pressure (BP) and uremic toxins are well-known risk factors for CVDs, which are influenced by diet. Dietary fiber supplementation in patients undergoing HD may reduce the risk of CVDs by improving lipid profiles and inflammatory status and lowering the levels of the uremic toxin indoxyl sulfate (IS). In this study, we investigated the relationship between the intestinal microbiota and risk factors for CVDs, such as BP and serum IS, in patients undergoing HD who consumed fruits granola (FGR). The study participants were selected from patients undergoing HD at the Izu Nagaoka Daiichi Clinic and consumed FGR for 2 months. Body composition and blood samples were tested at months 0, 1, 2 and fecal samples were collected at months 0 and 2 for intestinal microbiota analysis. FGR consumption decreased systolic and diastolic BP, estimated salt intake, and serum IS levels and improved the stool characteristics according to the Bristol Stool Form Scale (N = 24). Gut microbiota analysis showed an increase in the alpha diversity and abundance of Blautia and Neglecta. The abundance of lactic acid- and ethanol-producing bacteria also significantly increased, whereas the abundance of indole-producing bacteria significantly decreased. FGR consumption could be a useful tool for salt reduction, fiber supplementation, and improvement of the intestinal environment, thus contributing to improvement of BP and the reduction of other risk factors for CVDs in patients undergoing HD.

Chronic Kidney Disease (CKD), is often detected late due to its asymptomatic nature in the early stage of the disease. Overproduction of reactive oxygen species contributes to various pathological processes through oxidative stress (OS), impacting on cellular structures and functions with previous studies suggesting a link between OS and CKD progression. This study investigated the association between serum peroxiredoxin-4 (Prx4), a biomarker of oxidative stress, and the development of CKD in the general population.

This study featured data from the Prevention of REnal and Vascular ENd-stage Disease (PREVEND) cohort, involving 5341 participants without CKD at baseline who underwent extensive prospective health evaluations. Serum Prx4 levels were quantified using an immunoluminometric assay. The primary outcome was new-onset CKD as defined by the composite of urinary albumin excretion (UAE) > 30 mg/24-h, an estimated glomerular filtration rate (eGFR) < 60 mL/min/1.73 m2, or both.

Baseline median Prx4 level was 0.65 [interquartile range (IQR): 0.42-1.04] U/L, median eGFR was 98 [IQR: 87-108] mL/min/1.73 m2, and median UAE was 8.1 [IQR: 6.0-12.1] mg/L. During a median follow-up of 10.4 [IQR: 6.3-11.4] years, 867 (16.2 %) patients developed new-onset CKD. Higher Prx4 levels were significantly associated with an increased risk of CKD (hazard ratio (HR) per doubling: 1.29 [95 % confidence interval (CI): 1.21-1.37], p < 0.001), also after adjustment for risk factors including sex, smoking status, systolic blood pressure, high-sensitive C-reactive protein, chronic heart failure, diabetes mellitus and dyslipidemia (HR per doubling: 1.16 [1.06-1.24], p < 0.001). Sensitivity analyses confirmed the robustness of these findings.

This study supports the hypothesis that systemic oxidative stress, reflected by higher serum Prx4 levels, is significantly associated with the risk of developing CKD in the general population. These findings suggest that Prx4 could be a valuable biomarker for early risk stratification and prevention strategies in CKD management.

We previously demonstrated that the NO-receptor soluble guanylyl cyclase (GC1) has the ability to transnitrosate other proteins in a reaction that involves, in some cases, oxidized Thioredoxin 1 (oTrx1). This transnitrosation cascade was established in vitro and we identified by mass spectrometry and mutational analysis Cys 610 (C610) of GC1 α-subunit as a major donor of S-nitrosothiols (SNO). To assay the relevance of GC1 transnitrosation under physiological conditions and in oxidative pathologies, we studied a knock-in mouse in which C610 was replaced with a serine (KI αC 610S ) under basal or angiotensin II (Ang II)-treated conditions. Despite similar GC1 expression and NO-stimulated cGMP-forming activity, the Ang II-treated KI mice displayed exacerbated oxidative pathologies including higher mean arterial pressure and more severe cardiac dysfunctions compared to the Ang II-treated WT. These phenotypes were associated with a drastic decrease in global S-nitrosation and in levels of SNO-Trx1 and SNO-RhoA in the KI mice. To investigate the mechanism underlying the dysregulation of blood pressure despite an intact NO-cGMP axis, pressure myography and in vivo intravital microscopy were conducted to analyze the vascular resistance tone. Both approaches indicated that, even in the absence of oxidative stress, the single mutation C610S led to a significant deficiency in acetylcholine-induced vasorelaxation while smooth muscle relaxation in response to NO remained unchanged. These findings indicate that the C610S mutation uncoupled the two NO signaling pathways involved in the endothelium and smooth muscle vasorelaxation and suggest that GC1-dependent S-nitrosation is a key player in endothelium-derived hyperpolarization.

Normotensive and hypertensive organisms respond differently to stress factors; however, the features of the central molecular genetic mechanisms underlying the reaction of the hypertensive organism to stress have not been fully established. In this study, we examined the transcriptome profiles of the hypothalamus of hypertensive ISIAH rats, modeling a stress-sensitive form of arterial hypertension, and normotensive WAG rats at rest and after exposure to a single short-term restraint stress. It was shown that oxidative phosphorylation is the most significantly enriched process among metabolic changes in the hypothalamus of rats of both strains when exposed to a single short-term restraint stress. The analysis revealed DEGs representing both a common response to oxidative stress for both rat strains and a strain-specific response to oxidative stress for hypertensive ISIAH rats. Among the genes of the common response to oxidative stress, the most significant changes in the transcription level were observed in Nos1, Ppargc1a, Abcc1, Srxn1, Cryab, Hspb1, and Fosl1, among which Abcc1 and Nos1 are associated with hypertension, and Fosl1 and Ppargc1a encode transcription factors. The response to oxidative stress specific to hypertensive rats is associated with the activation of the Fos gene. The DEG's promoter region enrichment analysis allowed us to hypothesize that the response to oxidative stress may be mediated by the participation of the transcription factor CREB1 (Cyclic AMP-responsive element-binding protein 1) and the glucocorticoid receptor (NR3C1) under restraint stress in the hypothalamus of both rat strains. The results of the study revealed common and strain-specific features in the molecular mechanisms associated with oxidative phosphorylation and oxidative stress response in the hypothalamus of hypertensive ISIAH and normotensive WAG rats following a single short-term restraint stress. The obtained results expand the understanding of the most significant molecular targets for further research aimed at developing new therapeutic strategies for the prevention of the consequences of acute emotional stress, taking into account the hypertensive state of the patient.

Gestational diabetes mellitus (GDM) disrupts glucolipid metabolism, endangering maternal and fetal health. Despite limited research on its pathogenesis and treatments, we conducted a study using serum samples from GDM-diagnosed pregnant women. We performed metabolic sequencing to identify key small molecule metabolites and explored their molecular interactions with FGF21. We also investigated FGF21's impact on GDM using blood samples from affected women. Our analysis revealed a novel finding: elevated levels of L-Cystine in GDM patients. Furthermore, we observed a positive correlation between L-Cystine and FGF21 levels, and found that L-Cystine induces NRF2 expression via FGF21 for a period of 96 h. Under high glucose (HG) conditions, FGF21 upregulates NRF2 and downstream genes NQO1 and EPHX1 via AKT phosphorylation induced by activation of IRS1, enhancing endothelial function. Additionally, we confirmed that levels of FGF21, L-Cystine, and endothelial function at the third trimester were effectively enhanced through appropriate exercise and diet during pregnancy in GDM patients (GDM + ED). These findings suggest FGF21 as a potential therapeutic agent for GDM, particularly in protecting endothelial cells. Moreover, elevated L-Cystine via appropriate exercise and diet might be a potential strategy to enhance FGF21's efficacy.

This study investigated the association between the triglyceride-glucose (TyG) index, a surrogate marker of insulin resistance, and moderate/severe periodontitis and the role of blood pressure as a mediator in this association. A second aim was to assess the role of cardiometabolic conditions such as obesity, hypertension, and dyslipidemia as potential effect modifiers.

Data from 5733 US adults aged 30-64 years and with complete periodontal examination were analyzed (NHANES 2011-2014). Participants were classified as having moderate/severe periodontitis or mild/no periodontitis according to the CDC/AAP criteria as the outcome. The exposure was the TyG index, while both systolic (SBP), and diastolic (DBP) blood pressure were tested as mediators using parametric g-formula. Analyses were adjusted for relevant confounders, namely, age, sex, ethnicity, poverty-income ratio, and smoking, using inverse probability treatment weighting. Obesity status (based on a body mass index ≥30 kg/m2), self-report of hypertension and dyslipidemia (calculated based on the thresholds provided by National Cholesterol Education Program-Adult Treatment Panel-III) were tested as effect modifiers.

The findings showed the TyG index to be associated with increased odds of moderate/severe periodontitis [odds ratio (OR), 95% confidence interval (CI) = 1.17 (1.11-1.23)], with 50% of the total effect mediated by SBP. Stratified analysis showed a stronger association in individuals with obesity, hypertension, and dyslipidemia compared to those without these conditions. However, in those taking anti-hypertensive medications, the association was partially mitigated. Sensitivity analysis using imputed data showed consistent results.

The TyG index was associated with increased odds of moderate/severe periodontitis, especially in individuals with obesity, hypertension, and dyslipidemia. SBP levels partially mediated this association.

LCZ696 blocks both angiotensin receptor type 1 (ATR1) and neprilysin (NEP), which are intricate in the degradation of natriuretic peptides (NPs) and other endogenous peptides. It has been shown NEP inhibitors and LCZ696 could be effectively in the management of atherosclerosis (AS). However, the underlying mechanism of LCZ696 in AS is needed to be clarified entirely. Hence, this review is directed to reconnoiter the mechanistic role of LCZ696 in AS. The anti-inflammatory role of LCZ696 is related to the inhibition of transforming growth factor beta (TGF-β)-activated kinase 1 (TAK) and nod-like receptor pyrin 3 receptor (NLRP3) inflammasome. Moreover, LCZ696, via inhibition of pro-inflammatory cytokines, oxidative stress, apoptosis and endothelial dysfunction can attenuate the development and progression of AS. In conclusion, LCZ696 could be effective in the management of AS through modulation of inflammatory and oxidative signaling. Preclinical and clinical studies are recommended in this regard.

Oxidative stress plays a significant role in the pathogenesis of cardiovascular diseases, such as myocardial ischemia/reperfusion injury, atherosclerosis, heart failure, and hypertension. This systematic review aims to integrate most relevant studies on oxidative stress management in cardiovascular diseases. We searched relevant literatures in the PubMed database using specific keywords. We put emphasis on those manuscripts that were published more recently and in higher impact journals. We reviewed a total of 200 articles. We examined current oxidative stress managements in cardiovascular diseases, including supplements like resveratrol, vitamins C and E, omega-3 fatty acids, flavonoids, and coenzyme-10, which have shown antioxidative properties and potential cardiovascular benefits. In addition, we reviewed the pharmacological treatments including newly discovered antioxidants and nanoparticles that show potential effects in targeting the specific oxidative stress pathways. Lastly, we examined biomarkers, such as soluble transferrin receptor, transthyretin, and cystatin C in evaluating antioxidant status and identifying cardiovascular risk. By addressing oxidative stress management and mechanisms, this paper emphasizes the importance of maintaining the balance between oxidants and antioxidants in the progression of cardiovascular diseases. This review paper is registered with the International Platform of Registered Systematic Review and Meta-analysis Protocols (INPLASY), registration # INPLASY202470064.

Sickle cell disease (SCD) is the most severe monogenic hemoglobinopathy caused by a single genetic mutation that leads to repeated polymerization and depolymerization of hemoglobin resulting in intravascular hemolysis, cell adhesion, vascular occlusion, and ischemia-reperfusion injury. Hemolysis causes oxidative damage indirectly by generating reactive oxygen species through various pathophysiological mechanisms, which include hemoglobin autoxidation, endothelial nitric oxide synthase uncoupling, reduced nitric oxide bioavailability, and elevated levels of asymmetric dimethylarginine. Red blood cells have a built-in anti-oxidant system that includes enzymes like sodium dismutase, catalase, and glutathione peroxidase, along with free radical scavenging molecules, such as vitamin C, vitamin E, and glutathione, which help them to fight oxidative damage. However, these anti-oxidants may not be sufficient to prevent the effects of oxidative stress in SCD patients. Therefore, in line with a recent FDA request that the focus to be placed on the development of innovative therapies for SCD that address the root cause of the disease, there is a need for therapies that target oxidative stress and restore redox balance in SCD patients. This review summarizes the current state of knowledge regarding the role of oxidative stress in SCD and the potential benefits of anti-oxidant therapies. It also discusses the challenges and limitations of these therapies and suggests future directions for research and development.

Obstructive sleep apnea (OSA) is a common sleep-related breathing disorder. Its prevalence has increased due to increasing obesity and improved screening and diagnostic strategies. OSA overlaps with cardiopulmonary diseases to promote intermittent hypoxia and autonomic dysfunction. Intermittent hypoxia increases the risk for oxidative stress and inflammation, which promotes endothelial dysfunction and predisposes to atherosclerosis and other cardiovascular complications. OSA is associated with an increased sympathetic nervous system drive resulting in autonomic dysfunction leading to worsening of cardiopulmonary diseases. Cardiovascular diseases are observed in 40% to 80% of OSA patients. Therefore, it is essential to screen and treat cardiovascular diseases.

Given advances in antiretroviral therapy, the mortality rate for HIV infection has dropped considerably over recent decades. However, people living with HIV (PLWH) experience longer life spans coupled with persistent immune activation despite viral suppression and potential toxicity from long-term antiretroviral therapy use. Consequently, PLWH face a cardiovascular disease (CVD) risk more than twice that of the general population, making it the leading cause of death among this group. Here, we briefly review the epidemiology of CVD in PLWH highlighting disparities at the intersections of sex and gender, age, race/ethnicity, and the contributions of social determinants of health and psychosocial stress to increased CVD risk among individuals with marginalized identities. We then overview the pathophysiology of HIV and discuss the primary factors implicated as contributors to CVD risk among PLWH on antiretroviral therapy. Subsequently, we highlight the functional evidence of premature vascular dysfunction as an early pathophysiological determinant of CVD risk among PLWH, discuss several mechanisms underlying premature vascular dysfunction in PLWH, and synthesize current research on the pathophysiological mechanisms underlying accelerated vascular aging in PLWH, focusing on immune activation, chronic inflammation, and oxidative stress. We consider understudied aspects such as HIV-related changes to the gut microbiome and psychosocial stress, which may serve as mechanisms through which exercise can abrogate accelerated vascular aging. Emphasizing the significance of exercise, we review various modalities and their impacts on vascular health, proposing a holistic approach to managing CVD risks in PLWH. The discussion extends to critical future study areas related to vascular aging, CVD, and the efficacy of exercise interventions, with a call for more inclusive research that considers the diversity of the PLWH population.

The gut microbiome may affect overall cardiometabolic health. Enterolactone is an enterolignan reflective of dietary lignan intake and gut microbiota composition and diversity that can be measured in the urine. The purpose of this study was to examine the association between urinary enterolactone concentration as a reflection of gut health and blood pressure/risk of hypertension in a large representative sample from the US population. This analysis was conducted using data from the National Health and Nutrition Examination Survey (NHANES) collected from January 1999 through December 2010. Variables of interest included participant characteristics (including demographic, anthropometric and social/environmental factors), resting blood pressure and hypertension history, and urinary enterolactone concentration. 10,637 participants (45 years (SE = 0.3), 51.7% (SE = 0.6%) were female) were included in analyses. In multivariable models adjusted for demographic, socioeconomic and behavioral/environmental covariates, each one-unit change in log-transformed increase in enterolactone was associated with a 0.738 point (95% CI: -0.946, -0.529; p<0.001) decrease in systolic blood pressure and a 0.407 point (95% CI: -0.575, -0.239; p<0.001) decrease in diastolic blood pressure. Moreover, in fully adjusted models, each one-unit change in log-transformed enterolactone was associated with 8.2% lower odds of hypertension (OR = 0.918; 95% CI: 0.892, 0.944; p<0.001). Urinary enterolactone, an indicator of gut microbiome health, is inversely associated with blood pressure and hypertension risk in a nationally representative sample of U.S. adults.

Hypertensive diseases of pregnancy (HDPs) represent a global clinical challenge, affecting 5-10% of women and leading to complications for both maternal well-being and fetal development. At the heart of these complications is endothelial dysfunction, with oxidative stress emerging as a pivotal causative factor. The reduction in nitric oxide (NO) bioavailability is a vital indicator of this dysfunction, culminating in blood pressure dysregulation. In the therapeutic context, although antihypertensive medications are commonly used, they come with inherent concerns related to maternal-fetal safety, and a percentage of women do not respond to these therapies. Therefore, alternative strategies that directly address the pathophysiology of HDPs are required. This article focuses on the potential of the nitrate-nitrite-NO pathway, abundantly present in dark leafy greens and beetroot, as an alternative approach to treating HDPs. The objective of this review is to discuss the prospective antioxidant role of nitrate. We hope our discussion paves the way for using nitrate to improve endothelial dysfunction and control oxidative stress, offering a potential therapy for managing HDPs.

Genetic and environmental factors interact in a complex manner in the pathogenesis of essential hypertension in humans. Oxidative stress is considered one of the more important environmental factors. We used the spontaneously hypertensive rat (SHR) model to test whether continuous feeding with the antioxidant tempol reduces maternal oxidative stress during pregnancy and potentially contributes to the prevention of cardiovascular disease onset. Pregnant female rats were divided into control and tempol-treated groups. Tempol was continuously administered in drinking water. The administration period lasted approximately 40 days, from the confirmation of a vaginal plug until birth of the pups and their subsequent weaning. The blood pressure (BP) of each adult female was measured three times during pregnancy and post parturition. Milk was collected three times from nursing mother rats in the immediate postpartum period. Markers of oxidative stress were measured: 8-hydroxyl-2'-deoxyguanosine (8-OHdG) levels in milk during the experimental period and 8-OHdG and corticosterone levels in urine of adult and neonatal rats. The urinary level of 8-OHdG in the tempol-treated group was significantly lower than that in the control group. Corticosterone levels were significantly lower in urine of neonatal rats from the tempol-treated group compared with the levels of the control group. The levels of total antioxidant in milk were significantly greater in the tempol-treated group than in the control group. This study demonstrated that continuous administration of tempol to pregnant SHRs reduced maternal oxidative stress and contributed to reduced oxidative stress in neonatal rats.

Platelets are one of the coagulation cells. When platelet activation occurs, many mediators are released and affect endothelial cells (ECs) and lead to endothelial dysfunction (ED). ED plays an important role in the pathogenesis of many diseases, including cardiovascular disease (CVD). Platelet are of important factors in ED. The release of mediators by platelets causes the stimulation of inflammatory pathways, oxidative stress, and apoptosis, which ultimately result in ED.On the other hand, platelet activation in CVD patients can be associated with a bad prognosis. Platelet activation can increase the level of markers such as p-selectin in the serum. Also, in this study, we have discussed the role of platelet as a diagnostic factor, as well as its use as a treatment option. In addition, we discussed some of the molecular pathways that are used to target platelet activation.

Hypertension is the primary modifiable risk factor for cardiovascular, renal, and cerebrovascular diseases and is considered the main contributing factor to morbidity and mortality worldwide. Approximately 50% of hypertensive and 25% of normotensive people exhibit salt sensitivity of blood pressure, which is an independent risk factor for cardiovascular disease. Human and animal studies demonstrate that the immune system plays an important role in the etiology and pathogenesis of salt sensitivity of blood pressure, kidney damage, and vascular diseases. Antigen-presenting and adaptive immune cells are implicated in salt-sensitive hypertension and salt-induced renal and vascular injury. Elevated sodium activates antigen-presenting cells to release proinflammatory cytokines including IL (interleukin) 6, tumor necrosis factor-α, IL-1β, and accumulate isolevuglandin-protein adducts. In turn, these activate T cells release prohypertensive cytokines including IL-17A. Moreover, high-salt intake is associated with gut dysbiosis, leading to inflammation, oxidative stress, and blood pressure elevation but the mechanistic contribution to salt-sensitivity of blood pressure is not clearly understood. Here, we discuss recent advances in research investigating the cause, potential biomarkers, and therapeutic targets for salt-sensitive hypertension as they pertain to the gut microbiome, immunity, and inflammation.

This study aims to investigate the antihypertensive effect of four chicken muscle-derived angiotensin (Ang)-converting enzymes (ACE)-regulating peptides: Val-Arg-Pro (VRP, ACE inhibition), Leu-Lys-Tyr and Val-Arg-Tyr (LKY and VRY, ACE inhibition and ACE2 upregulation), and Val-Val-His-Pro-Lys-Glu-Ser-Phe (VVHPKESF [V-F], ACE2 upregulation) in spontaneously hypertensive rats.

Rats (12-14 weeks old) are grouped: 1) untreated, 2) VRP, 3) LKY, 4) VRY, and 5) V-F. Blood pressure (BP) is monitored using implantable telemetry technology. Over 18-day oral administration of 15 mg kg-1 body weight (BW) per day, only peptide V-F significantly (p < 0.05) reduces BP, decreases circulating Ang II, and increases ACE2 and Ang (1-7) levels, and enhances aortic expressions of ACE2 and Mas receptor (MasR). Peptide V-F also attenuates vascular inflammation (TNFα, MCP-1, IL-1α, IL-15, and cyclooxygenase 2 [COX2]) and vascular oxidative stress (nitrotyrosine). The gastrointestinal (GI)-degraded fragment of peptide V-F, Val-Val-His-Pro-Lys (VVHPK), is also an ACE2-upregulating peptide. Peptides VRP, LKY, and VRY do not reduce BP, possibly due to low bioavailability or other unknown reasons.

Peptide V-F is the first ACE2-upregulating peptide, purified and fractionated from food proteins based on in vitro ACE2 upregulation, that reduces BP associated with the activation of ACE2/Ang (1-7)/MasR axis; the N-terminal moiety VVHPK may be responsible for the antihypertensive effect of V-F.

Chlorella supplementation is reported to improve V˙O2max following extended supplementation periods (~3 weeks). However, there is little research on its impact over submaximal exercise intensities and following shorter supplementation regimens. This study aimed to investigate the efficacy of 6 g/day 2-day chlorella supplementation on exercise performance in healthy young adults. Twenty young healthy adults (Males = 16, Females = 4) (Age 22 ± 6 years, V˙O2max 42.7 ± 9.6 mL/(kg·min)) were recruited for this double-blinded, randomised cross-over study. Participants ingested 6 g/day of chlorella or a placebo for 2 days, with a one-week washout period between trials. Exercise testing consisted of a 20 min submaximal cycle at 40% of their work rate max (WRmax) (watts), followed by an incremental V˙O2max test. Lactate (mmol/L), heart rate (b/min), oxygen consumption (mL/(kg·min)), O2 pulse (mL/beat), respiratory exchange ratio (RER), and WRmax were compared across conditions. Following chlorella supplementation, blood lactate levels were significantly lower (p < 0.05) during submaximal exercise (3.05 ± 0.92 mmol/L vs. 2.67 ± 0.79 mmol/L) and following V˙O2max tests (12.79 ± 2.61 mmol/L vs. 11.56 ± 3.43 mmol/L). The O2 pulse was significantly higher (p < 0.05) following chlorella supplementation during submaximal (12.6 ± 3.5 mL/beat vs. 13.1 ± 3.5 mL/beat) and maximal exercise intensity (16.7 ± 4.6 mL/beat vs. 17.2 ± 4.5 mL/beat). No differences existed between conditions for oxygen consumption, RER, V˙O2max, or WRmax. A total of 2 days of 6 g/day chlorella supplementation appears to lower the blood lactate response and increase O2 pulse during both submaximal and maximal intensity exercise but did not lead to any improvements in V˙O2max.

Oxidative stress is implicated in the development and progression of type 2 diabetes (T2D). Peroxiredoxin-4 is an antioxidant protein, which may serve as biomarker of oxidative stress, and has previously been associated with new-onset T2D. In this study, we investigated associations between circulating peroxiredoxin-4 and the risk of developing new-onset microvascular complications in T2D patients. Serum peroxiredoxin-4 was measured in 536 patients with T2D with (n = 257) and without (n = 279) baseline microvascular complications who participated in a primary-care based cohort study (Zwolle Outpatient Diabetes project Integrating Available Care [ZODIAC] study). Over a median follow-up of 3.4 years, 38 (13.6%) developed nephropathy, defined as albuminuria in two consecutive urine samples. In multivariable Cox proportional hazards regression analyses, peroxiredoxin-4 was associated with new-onset nephropathy (hazard ratio [HR] per doubling 1.78 [95% CI: 1.27-2.49], P < 0.001) after adjustment for potential confounding factors, including age, sex, disease duration, HbA1c levels, macrovascular complications, systolic blood pressure, and even high-sensitive C-reactive protein. There was no interaction of peroxiredoxin-4 with hs-CRP impacting on new-onset nephropathy. No significant associations were found with new-onset retinopathy or neuropathy. In conclusion, circulating peroxiredoxin-4 associates positively with an increased risk of developing nephropathy in T2D independent and irrespective of low-grade inflammation.