Vascular endothelial cells (ECs) play a key role in physiology by controlling arterial contraction and relaxation, and molecular transport. EC dysfunction is associated with multiple pathologies. Here, we characterize the cellular and extracellular matrix (ECM) proteomes of primary human coronary artery ECs, from multiple donors, and oxidation/nitration products formed on these during cell culture, using liquid chromatography-mass spectrometry. In total ∼9900 proteins were identified in cells from 3 donors, with ∼7000 proteins per donor. Of these ∼5300 were consistently identified, indicating some heterogeneity across the donors, with age a possible cause. Multiple endogenous oxidation products were detected on both ECM and cellular proteins (and particularly endoplasmic reticulum species). In contrast, nitration was mostly detected on cell proteins and particularly cytoskeletal proteins, consistent with intracellular generation of nitrating agents, possibly from endothelial nitric oxide synthase (eNOS) or peroxidase enzymes. The modifications are ascribed to both physiological enzymatic activity (hydroxylation at proline/lysine; predominantly on ECM proteins and especially collagens) and the formation of reactive species (oxidation at tryptophan/tyrosine/histidine; nitration at tryptophan/tyrosine). The identified sites are present on a limited number of peptides (104 oxidized; 23 nitrated) from a modest number of proteins. A small number of proteins were detected with multiple modifications, consistent with these being selective and specific targets. Several nitrated peptides were consistently detected across all donors, and also in human smooth muscle cells suggesting that these are major targets in the vascular proteome. These data provide a 'background' proteome dataset for studies of endothelial dysfunction in disease.

The formation of a blood vessel network is crucial for organ development and regeneration. Over the past three decades, the central molecular mechanisms governing blood vessel growth have been extensively studied. Recent evidence indicates that vascular endothelial cells-the specialized cells lining the inner surface of blood vessels-exhibit significant heterogeneity to meet the specific needs of different organs. This review focuses on the current understanding of endothelial cell heterogeneity, which includes both intra-organ and inter-organ heterogeneity. Intra-organ heterogeneity encompasses arterio-venous and tip-stalk endothelial cell specialization, while inter-organ heterogeneity refers to organ-specific transcriptomic profiles and functions. Advances in single-cell RNA sequencing (scRNA-seq) have enabled the identification of new endothelial subpopulations and the comparison of gene expression patterns across different subsets of endothelial cells. Integrating scRNA-seq with other high-throughput sequencing technologies promises to deepen our understanding of endothelial cell heterogeneity at the epigenetic level and in a spatially resolved context. To further explore human endothelial cell heterogeneity, vascular organoids offer powerful tools for studying gene function in three-dimensional culture systems and for investigating endothelial-tissue interactions using human cells. Developing organ-specific vascular organoids presents unique opportunities to unravel inter-organ endothelial cell heterogeneity and its implications for human disease. Emerging technologies, such as scRNA-seq and vascular organoids, are poised to transform our understanding of endothelial cell heterogeneity and pave the way for innovative therapeutic strategies to address human vascular diseases.

Acute kidney injury (AKI) is a clinical challenge characterized by elevated morbidity and a substantial impact on individual health and socioeconomic factors. A comprehensive examination of the molecular pathways behind AKI is essential for its prevention and management. In recent years, vigorous research in the domain of AKI has concentrated on pathophysiological characteristics, early identification, and therapeutic approaches across many aetiologies and highlighted the principal themes of oxidative stress, inflammatory response, apoptosis, necrosis, and immunological response. This review comprehensively reviewed the molecular mechanisms underlying AKI, including oxidative stress, inflammatory pathways, immune cell-mediated injury, activation of the renin-angiotensin-aldosterone (RAAS) system, mitochondrial damage and autophagy, apoptosis, necrosis, etc. Inflammatory pathways are involved in the injuries in all four structural components of the kidney. We also summarized therapeutic techniques and pharmacological agents associated with the aforementioned molecular pathways. This work aims to clarify the molecular mechanisms of AKI thoroughly, offer novel insights for further investigations of AKI, and facilitate the formulation of efficient therapeutic methods to avert the progression of AKI.

In a global context of escalating multimorbidity, characterized by the co-occurrence of major depressive disorder (MDD), endothelial dysfunction (ED), and gastrointestinal dysregulation (GD), the quest for effective treatments has become paramount. Central to these interconnected conditions is oxidative stress (OS), a pivotal factor that has been extensively studied yet remains inadequately addressed. This study introduces Chaihu-Shugan-San (CSS) and its absorbed component ferulic acid (FA), a potent antioxidant derived from medicinal plants, as a novel therapeutic approach with the unique ability to counter the multifaceted effects of acute forced swimming (AFS)-induced depression, ED, and GD. Unlike traditional single-disease-focused studies, our research explores the synergistic effects of CSS and FA across these interrelated disorders, offering a groundbreaking perspective.

This study aims to evaluate CSS and FA in treating depression-related multimorbidity triggered by AFS and to uncover the shared underlying mechanisms of FA.

A depression-like model in rats was induced by AFS, and an OS model was established in endothelial cells (ECs) through hydrogen peroxide treatment. We investigated the effects of CSS and FA on MDD, ED, and GD in rats and OS levels in ECs. Our assessments included hematoxylin and eosin (HE) staining, biochemical assays, and behavioral studies. We conducted an integrated analysis of transcriptomics, proteomics, and phosphoproteomics data to elucidate the underlying mechanisms. The identification of relevant targets was confirmed through Western blotting (WB), real-time quantitative polymerase chain reaction (RT-qPCR), molecular docking studies, and an extensive literature review.

Our findings indicate that CSS and FA not only significantly mitigate AFS-induced abnormalities in the open field test (OFT), forced swim test (FST), and related behaviors such as gastric emptying and intestinal transit in rats but also ameliorate depression, ED, GD, inflammation and OS-related biomarker levels, alongside HE staining in gastric sinus and aorta slices. The study also highlights that FA can influence OS and endothelial function in ECs. Moreover, a combined multi-omics analysis unveiled several OS-related pathways, including the mTOR and p53 signaling pathways. Our research elucidates that the Ghrl-Edn1/Mecp2/P-mTOR/Vegfa-associated OS signaling pathway is pivotal in countering AFS-induced multimorbidity, expanding beyond the conventional disease-specific focus.

This pioneering study underscores capability of CSS and FA to tackle AFS-induced multimorbidity concurrently and intricately details FA's antioxidative mechanisms within ECs. The insights gleaned offer a novel perspective on FA's role in multimorbidity regulation and its potential to modulate OS, especially in the complex environment of ECs. Given the urgent global health challenges, our research positions FA as a promising therapeutic contender, advocating for a paradigm shift in multimorbidity management.

To date, an increasing body of evidence supports the potential role of activated platelets in the pathogenesis of non-alcoholic fatty liver disease (NAFLD). This is likely due to their ability to secrete biologically active substances that regulate liver regeneration processes, ensure hemostasis, and participate in the immune response. Additionally, several studies have demonstrated the efficacy of antiplatelet agents in reducing inflammation, the severity of liver fibrosis, and the progression of fibrosis in non-alcoholic steatohepatitis (NASH). Since NAFLD is not an independent indication for antiplatelet therapy, the primary evidence regarding their efficacy in NAFLD has been derived from studies using animal models of NAFLD or in patients with concomitant cardiovascular diseases. This narrative review will discuss the main functions of platelets, their unique interactions with liver cells, and the outcomes of these interactions, as well as the results of studies evaluating the efficacy and safety of antiplatelet therapy in patients with NAFLD.

Background: Ischemic heart disease remains the leading cause of death worldwide, with coronary microvascular dysfunction (CMD) as a key complication after ST-elevation myocardial infarction (STEMI). Endothelial dysfunction contributes to CMD, impairing vascular tone and increasing inflammation. While angiotensin-converting enzyme (ACE) inhibitors and angiotensin II receptor blockers (ARBs) aid vascular health, their efficacy may improve with therapeutic ultrasound, which enhances drug delivery and endothelial response. This study explores the combined effects of ultrasound and pharmacological treatment on the ACE axis and inflammation in endothelial and renal cells. Methods: Human umbilical vein endothelial cells (HUVECs) and human renal proximal tubular epithelial cell line RPTEC/TERT1 were treated with captopril, losartan, and dexamethasone, alone or combined with low-frequency ultrasound (LFU). Cell viability and wound-healing assays assessed cellular function, while nitric oxide (NO) and reactive oxygen species (ROS) assays were used to evaluate redox signaling. Gene expression related to the ACE axis, inflammation, and vascular and renal cell function was analyzed via qPCR. Results: Captopril and losartan combined with LFU improved endothelial cell viability, wound healing, and NO production at various concentrations, whereas only losartan with LFU enhanced cell viability and wound healing in renal cells. Dexamethasone with LFU increased ROS levels and had variable effects on RPTEC/TERT1 cell survival. Gene expression analysis showed that LFU alone reduced pro-inflammatory markers VCAM-1, ICAM-1, and PTGS2 in captopril-treated HUVECs and similarly affected CYP4F2 in losartan-treated HUVECs. LFU also decreased PTGS2 expression at higher dexamethasone concentrations. In RPTEC/TERT1 cells, LFU alone did not impact SGLT2 or GGT1 expression, but captopril with LFU downregulated GGT1, and dexamethasone with LFU upregulated SGLT2 at higher concentrations. Conclusions: This study demonstrates that LFU enhances the effects of RAS inhibitors by promoting NO synthesis and reducing oxidative stress, while its combination with dexamethasone may have variable, potentially cytotoxic effects on renal cells. Gene expression patterns suggest LFU's anti-inflammatory potential and its role in modulating drug efficacy.

The occurrence of venous diseases among adults is approximately 77% in females and 57% in males. These conditions are prevalent, progressive disorders that significantly affect individuals socially, physically, and psychologically, often resulting in various venous abnormalities that hinder effective blood circulation in the lower limbs. This review provides a comprehensive overview of venous diseases, focusing on their pathophysiology, symptoms, causes, risk factors, diagnosis, and complications. The symptoms associated with venous diseases are diverse and can include pain, heaviness, swelling, ulcers, and skin changes. Risk factors such as age, obesity, hormonal influences, and genetic predispositions are discussed in relation to their contribution to disease progression. The therapeutic modalities for managing venous diseases are explored, with a particular emphasis on natural products in alleviating symptoms and improving vascular health. Natural compounds, i.e., flavonoids, play a vital role in the circulatory system, supporting blood vessels and promoting healthy blood flow, in addition to their vasoprotective, antioxidant, anti-inflammatory, and anti-platelet properties. Overall, the ongoing research efforts on the efficacy of natural products will significantly enhance the management of several venous diseases in the coming years.

Sleep deprivation is a growing concern in cardiovascular risk, causing physiological disruptions like autonomic dysregulation and inflammation. Recent research indicates that sleep deprivation increases sympathetic nervous activity while decreasing parasympathetic activity, leading to increased blood pressure, impaired endothelial function, and heightened inflammation. Exercise has emerged as a non-pharmacological approach to increase cardiovascular health. However, the impact of exercise on sleep deprivation-induced changes in autonomic activity and inflammation remains unclear. To explore this, we reviewed studies investigating the effects of acute exercise on autonomic regulation and inflammatory markers following sleep deprivation. We conducted a narrative review of the literature. PubMed/MEDLINE, Google Scholar, and Web of Science (WOS) searched the articles between May 2022 and April 2023. The papers had to: [1] focus on recent studies between 2000 and 2023; [2] consist of sleep deprivation participants; [3] be published in English. Acute moderate- to high-intensity exercise after sleep deprivation may reduce parasympathetic activity, trigger pro-inflammatory cytokines, and delay recovery to normal levels. In contrast, regular exercise routines may mitigate the adverse effects of sleep deprivation on autonomic regulation and reduce systemic inflammation. Sleep deprivation can lead to autonomic imbalance, increased blood pressure, and increased inflammatory responses, which are further amplified by acute exercise, increasing the cardiovascular burden. When sleep deprivation occurs, exercise intensity and timing should be carefully chosen to avoid adverse cardiovascular health risks.

Intrauterine adhesions (IUAs), also known as Asherman's syndrome (AS), represent a significant cause of uterine infertility for which effective treatment remains elusive. The endometrium's ability to regenerate cyclically depends heavily on the growth and regression of its blood vessels. However, trauma to the endometrial basal layer can disrupt the subepithelial capillary plexus, impeding regeneration. This damage results in the replacement of native cells with fibroblasts and myofibroblasts, ultimately leading to fibrosis. Endothelial cells (ECs) play a pivotal role in the vascular system, extending beyond their traditional barrier function. Through single-cell sequencing and experimental validation, we discovered that ECs undergo senescence in IUA patients, impairing angiogenesis and fostering stromal cell fibrosis. Further analysis revealed significant interactions between ECs and PAI-1+ stromal cells. PAI-1, derived from stromal cells, promotes EC senescence via the urokinase-type plasminogen activator receptor (uPAR). Notably, prior to fibrosis onset, TGF-β upregulates PAI-1 expression in stromal cells in a SMAD dependent manner. In an IUA mouse model, inhibiting PAI-1 mitigated EC senescence and endometrial fibrosis. Our findings underscore the crucial role of EC senescence in IUA pathogenesis, contributing to vascular reduction and fibrosis. Targeting PAI-1 represents a promising therapeutic strategy to suppress EC senescence and alleviate endometrial fibrosis, offering new insights into the treatment of IUAs.

von Willebrand factor (vWF) is a large multimeric sialoglycoprotein that plays key roles in normal haemostasis, inflammation regulation, angiogenesis and cancer metastasis in mammals. The gene, protein sequences and functions of vWF in flounder Paralichthys olivaceus (PovWF) were analysed in this study. PovWF possesses an 8550-bp open reading frame (ORF) that encodes a 2849 amino acid protein. PovWF mRNA is highly expressed in the heart and gill, followed by the intestine, skin, spleen, kidney, muscle and liver. PovWF positive cells are mainly endothelial cells (ECs), predominantly located along the inner lining of blood vessels, enclosing the bloodstream. After being infected with hirame novirhabdovirus (HIRRV), flounder exhibits a dark body colour, congested fins and visceral membranes. Histopathologic analysis revealed that the ECs of diseased fish had compromised integrity, accompanied by a significant increase in number of cells within blood vessels. Immunofluorescence and ultrastructural studies showed that virions infect ECs can induce morphological and functional alterations, which lead to the release of vWF and facilitate the migration of neutrophils into tissues to exert antiviral functions. This research pinpoints the role of vWF in the immune response to HIRRV infection in teleost. It offers an in-depth and all-encompassing understanding of the pathophysiological interaction between HIRRV and endothelial cells during invasive infections in fish.

Angiogenesis, a meticulously regulated process essential for both normal development and pathological conditions, necessitates a comprehensive understanding of the endothelial mechanisms governing its progression. Leveraging the zebrafish model and NgAgo knockdown system to identify target genes influencing angiogenesis, our study highlights the significant role of gastric inhibitory polypeptide (GIP) and its receptor (GIPR) in this process. While GIP has been extensively studied for its insulinotropic and glucagonotropic effects, its role in angiogenesis remains unexplored. This study demonstrated that GIPR knockdown induced developmental delays, morphological abnormalities, and pronounced angiogenic impairments in zebrafish embryos. Conversely, exogenous D-Ala2-GIP administration enhanced blood vessel formation in the yolk sac membrane of chick embryos. Consistent with these findings, D-Ala2-GIP treatment promoted microvessel formation in the tube formation assays and rat aortic ring models. Further investigation revealed that D-Ala2-GIP facilitated human umbilical vein endothelial cell (HUVEC) migration, a key step in angiogenesis, through the cyclic adenosine monophosphate (cAMP)-mediated activation of the Epac/Rap1/Cdc42 signaling pathway. This study provides novel insights into the angiogenic functions of GIP and its potential implications for cardiovascular biology.

Dysfunctions within the liver system are intricately linked to the progression of diabetic retinopathy (DR) and non-alcoholic fatty liver disease (NAFLD). This study leverages systematic analysis to elucidate the complex cross-talk and communication pathways among diverse cell populations implicated in the pathogenesis of DR and NAFLD.

Single-cell RNA sequencing data for proliferative diabetic retinopathy (PDR) and NAFLD were retrieved from the Gene Expression Omnibus (GEO) database. Differential gene expression analysis was conducted and followed by pseudo-time analysis to delineate dynamic changes in core cells and differentially expressed genes (DEGs). CellChat was employed to predict intercellular communication and signaling pathways. Additionally, gene set enrichment and variation analyses (GSEA and GSVA) were performed to uncover key functional enrichments.

Our comparative analysis of the two datasets focused on T cells, macrophages and endothelial cells, revealing SYNE2 as a notable DEG. Notably, common genes including PYHIN1, SLC38A1, ETS1 (T cells), PPFIBP1, LIFR, HSPG2 (endothelial cells), and MSR1 (macrophages), emerged among the top 50 DEGs across these cell types. The CD45 signaling pathway was pivotal for T cells and macrophages, exerting profound effects on other cells in both PDR and NAFLD. Moreover, GSEA and GSVA underscored their involvement in cellular communication, immune modulation, energy metabolism, mitotic processes.

The comprehensive investigation of T cells, macrophages, endothelial cells, and the CD45 signaling pathway advances our understanding of the intricate biological processes underpinning DR and NAFLD. This research underscores the imperative of exploring immune-related cell interactions, shedding light on novel therapeutic avenues in these disease contexts.

Bone is a highly calcified and vascularized tissue. The vascular system plays a vital role in supporting bone growth and repair, such as the provision of nutrients, growth factors, and metabolic waste transfer. Moreover, the additional functions of the bone vasculature, such as the secretion of various factors and the regulation of bone-related signaling pathways, are essential for maintaining bone health. In the bone microenvironment, bone tissue cells play a critical role in regulating angiogenesis, including osteoblasts, bone marrow mesenchymal stem cells (BMSCs), and osteoclasts. Osteogenesis and bone angiogenesis are closely linked. The decrease in osteogenesis and bone angiogenesis caused by aging leads to osteoporosis. Long noncoding RNAs (lncRNAs) are involved in various physiological processes, including osteogenesis and angiogenesis. Recent studies have shown that lncRNAs could mediate the crosstalk between angiogenesis and osteogenesis. However, the mechanism by which lncRNAs regulate angiogenesis‒osteogenesis crosstalk remains unclear. In this review, we describe in detail the ways in which lncRNAs regulate the crosstalk between osteogenesis and angiogenesis to promote bone health, aiming to provide new directions for the study of the mechanism by which lncRNAs regulate bone metabolism.

Hyperhomocysteinemia (HHcy) is associated with the development and progression of chronic cardiovascular diseases through the deleterious effects of high levels of homocysteine (Hcy) on the cardiovascular system. However, the exact mechanism of action of Hcy on the acute injury of the cardiovascular system following ischemia/reperfusion (I/R) remains unclear. The present study demonstrated that copper mobilization occurs during cardiac I/R, and the interactive toxic effect of Hcy and mobile Cu2+ during cardiac I/R induces necroptosis of cardiac microvascular endothelial cells (CMECs) and thus enhances cardiac dysfunction. In the present study, we utilized three cardiac I/R model: isolated rat heart, in vivo model as well as cell culture, and demonstrated that copper mobilization occurs during cardiac I/R, and the interactive toxic effect of Hcy and mobile Cu2+ during cardiac I/R induces necroptosis of cardiac microvascular endothelial cells (CMECs) and thus enhances cardiac dysfunction. Furthermore, we proved that the Cu2+ chelator TTM significantly mitigated the deleterious effects of Hcy and Cu2+ on CMECs and cardiac function both in vitro and in vivo. Mechanismly, the combinative effect of Hcy and Cu2+ are associated with the production of reactive oxygen species (ROS) and nitric oxide (NO) by NADPH oxidase (NOX) and endothelial nitric oxide synthase (eNOS), respectively. Subsequently, the overproduction of toxic peroxynitrite (ONOO-) induces CMECs necroptosis. The application of ROS scavengers in CMECs resulted in a notable reduction in necroptosis mediated by Hcy and Cu2+ under hypoxia/reperfusion (H/R) condition. These findings indicate that the mechanism by which Hcy and Cu2+ enhances cardiac dysfunction under I/R condition may be attributed to the stimulation of both NOX and eNOS activity, resulting in the generation of excessive ONOO- and subsequent necroptosis of CMECs.

Flagellar-driven locomotion plays a critical role in the bacterial attachment and colonization of surfaces, contributing to the risks of contamination and infection. Extensive efforts to uncover the underlying principles governing bacterial motility near surfaces have relied on idealized assumptions about surrounding artificial surfaces. However, in the context of living systems, the role of cells from tissues and organs becomes increasingly critical, particularly in bacterial swimming and adhesion, yet it remains poorly understood. Here, we propose using biological surfaces composed of vascular endothelial cells to experimentally investigate bacterial motion and interaction behaviors. Our results reveal that bacterial trapping observed on inorganic surfaces is counteractively manifested with reduced radii of circular motion on cellular surfaces. Additionally, two distinct modes of bacterial adhesion were identified: tight and loose adhesion. Interestingly, the presence of living cells enhances bacterial surface enrichment, and imposed flow intensifies this accumulation via a bias-swimming effect. These results surprisingly indicate that physical effects remain the dominant factor regulating bacterial motility and accumulation at the single-cell-layer level in vitro, bridging the gap between simplified hydrodynamic mechanisms and complex biological surfaces with relevance to biofilm formation and bacterial contamination.

The lateral thoracic artery (LTA) is one of six main branches that originate from the axillary artery. The LTA has a textbook origin from the 2nd part of the axillary artery posterior to the pectoralis minor muscle. Contrary to the textbook origin, there are numerous reports of LTA variants that originate from the thoracoacromial artery, subscapular artery, and thoracodorsal artery, or even its duplication. This case report involves description of an additional unique duplicate variant of the LTA, bilaterally. The right duplicate LTA has its origin from the 3rd part of the axillary artery and then courses with the axillary sheath before coursing towards the breast. The right duplicate LTA variant also gives off two small subcutaneous branches in the medial upper arm. The left duplicate LTA has its origin from the brachial artery and courses directly to the breast through the axilla. Additional detail on the variants of the LTA could prove useful in surgical procedures that involve the lateral thorax, chest, and axilla and contribute to broader anatomical knowledge.

The endothelium is pivotal in multiple physiological processes, such as maintaining vascular homeostasis, metabolism, platelet function, and oxidative stress. Emerging evidence in the past decade highlighted the immunomodulatory function of endothelium, serving as a link between innate, adaptive immunity and inflammation. This review examines the regulation of the immune-inflammatory axis by the endothelium, discusses physiological immune functions, and explores pathophysiological processes leading to endothelial dysfunction in various metabolic disturbances, including hyperglycemia, obesity, hypertension, and dyslipidaemia. The final section focuses on the novel, repurposed, and emerging therapeutic targets that address the immune-inflammatory axis in endothelial dysfunction.

Many patients with liver diseases are exposed to the risk of hepatic encephalopathy (HE). The incidence of HE in liver patients is high, showing various symptoms ranging from mild symptoms to coma. Liver transplantation is one of the ways to overcome HE. However, not all patients can receive liver transplantation. Moreover, patients who have received liver transplantation have limitations in that they are vulnerable to hepatocellular carcinoma, allograft rejection, and infection. To find other therapeutic strategies, it is important to understand pathological factors and mechanisms that lead to HE after liver disease. Oxidative stress, inflammatory response, hyperammonaemia and metabolic disorders seen after liver diseases have been reported as risk factors of HE. These are known to affect the brain and cause HE. These peripheral pathological factors can impair the blood-brain barrier, cause it to collapse and damage the neurovascular unit component of multiple cells, including vascular endothelial cells, astrocytes, microglia, and neurons, leading to HE. Many previous studies on HE have suggested the impairment of neurovascular unit and cell-cell communication in the pathogenesis of HE. This review focuses on pathological factors that appear in HE, cell type-specific pathological mechanisms, miscommunication/incorrect relationships, and therapeutic candidates between brain cells in HE. This review suggests that regulating communications and interactions between cells may be important in overcoming HE.

Objective: The aim of this study is to explore the protective mechanism of proline hydroxylase (PHD) in reducing myocardial ischemia-reperfusion injury (MIRI) through the hypoxia-inducible factor (HIF)-1α-adenosine-MAPK/ERK signaling pathway, with the goal of identifying potential drug targets and therapeutic strategies for the clinical management of MIRI. Methods: A rat model of MIRI was established using 45 male Sprague-Dawley (SD) rats, which were randomly divided into the following three groups: sham operation (n = 15), MIRI model (n = 15), and MIRI + FG-4592 preconditioning (n = 15) groups. Cardiac function was assessed by echocardiographic measurements of the left ventricular end-diastolic diameter (LVIDd), left ventricular contractile diameter (LVIDs), left ventricular shortening fraction (FS), and left ventricular ejection fraction (EF). Cardiomyocyte apoptosis was evaluated using hematoxylin-eosin (HE) and terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) staining. Myocardial infarct size was determined with 23,5-triphenyltetrazolium chloride (TTC) staining, while levels of inflammatory factors such as interleukin-6 (IL-6), interleukin-1β (IL-1β), and tumor necrosis factor-α (TNF-α) were quantified using enzyme-linked immunosorbent assays (ELISA). Western blot (WB) analysis was performed to assess the expression of apoptotic proteins ERK1/2, phosphorylated-ERK1/2 (p-ERK1/2), AKT, phosphorylated-AKT (p-AKT), caspase-3, BCL-2, and BAX in the infarct boundary area. Adenosine levels within myocardial tissue were also measured. Results: FG-4592 preconditioning significantly improved cardiac function, lowered cardiomyocyte apoptosis and myocardial infarction size, reduced myocardial tissue damage, and inhibited inflammation. Additionally, FG-4592 increased the expression of anti-apoptotic proteins and enhanced adenosine levels in myocardial tissue in the treatment group compared with the MIRI model group. Conclusions: Inhibition of HIF-1α degradation plays a significant role in enhancing extracellular adenosine levels and reducing MIRI, possibly regulating apoptosis through the MAPK/ERK signaling pathway. These findings highlight the potential of targeting the PHD-HIF-adenosine axis in developing treatment strategies for MIRI, meriting future exploration.

Atherosclerosis is a chronic progressive disease which is known to cause acute cardiovascular events as well as cerebrovascular events with high mortality. Unlike many other diseases, atherosclerosis is often diagnosed only after an acute or fatal event. At present, the clinical problems of atherosclerosis mainly involve the difficulty in confirming the plaques or identifying the stability of the plaques in the early phase. In recent years, the development of nanotechnology has come with various advantages including non-invasive imaging enhancement, which can be studied for the imaging of atherosclerosis. For targeted imaging and atherosclerosis treatment, nanoliposomes provide enhanced stability, drug administration, extended circulation, and less toxicity. This review discusses the current advances in the development of tailored liposomal nano-radiopharmaceutical-based techniques and their applications to atherosclerotic plaque diagnosis. This review further highlights liposomal nano-radiopharmaceutical localisation and biodistribution-key processes in the pathophysiology of atherosclerosis. Finally, this review discusses the direction and future of liposomal nano-radiopharmaceuticals as a potential clinical tool for the assessment and diagnosis of atherosclerotic plaque.

Panvascular disease is characterized by the involvement of blood vessels across multiple regions of the body, and is associated with high morbidity, disability, and mortality rates. Its pathogenesis is multifaceted, necessitating risk assessment and treatment approaches that differ from those applied to single-organ diseases. Given that panvascular disease affects multiple vital organs, an integrated, multi-system management strategy offers significant advantages over conventional, organ-specific approaches. This article provides a comprehensive review of the epidemiological features, traditional and emerging risk factors, pathophysiological mechanisms, screening and risk assessment methods, as well as new strategies for the prevention and management of panvascular disease. The objective is to offer a theoretical foundation and technical support for enhancing prevention and control measures for this condition.

Endothelial dysfunction is a significant factor in the pathogenesis of various diseases. In pathological states, endothelial cells (ECs) undergo activation, resulting in dysfunction characterized by the stimulation of inflammatory responses, oxidative stress, cell proliferation, blood coagulation, and vascular adhesions. Interleukin-35 (IL-35), a novel member of the IL-12 family, is primarily secreted by regulatory T cells (Tregs) and regulatory B cells (Bregs). The role of IL-35 in immunomodulation, antioxidative stress, resistance to apoptosis, control of EC activation, adhesion, and angiogenesis in ECs remains incompletely understood, as the specific mechanisms of IL-35 action and its regulation have yet to be fully elucidated. Therefore, this systematic review aims to comprehensively investigate the impact of IL-35 on ECs and their physiological roles in a range of conditions, including cardiovascular diseases, tumors, sepsis, and rheumatoid arthritis (RA), with the objective of elucidating the potential of IL-35 as a therapeutic target for these ailments.

Advances in biofabrication have enabled the generation of freeform perfusable networks mimicking vasculature. However, key challenges remain in the effective endothelialization of these complex, vascular-like networks, including cell uniformity, seeding efficiency, and the ability to pattern multiple cell types. To overcome these challenges, we present an integrated fabrication and endothelialization strategy to directly generate branched, endothelial cell-lined networks using a diffusion-based, embedded 3D bioprinting process. In this strategy, a gelatin microparticle sacrificial ink delivering both cells and crosslinkers is extruded into a crosslinkable gel precursor support bath. A self-supporting, perfusable structure is formed by diffusion-induced crosslinking, after which the sacrificial ink is melted to allow cell release and adhesion to the printed lumen. This approach produces a uniform cell lining throughout networks with complex branching geometries, which are challenging to uniformly and efficiently endothelialize using conventional perfusion-based approaches. Furthermore, the biofabrication process enables high cell viability (>90%) and the formation of a confluent endothelial layer providing vascular-mimetic barrier function and shear stress response. Leveraging this strategy, we demonstrate for the first time the patterning of multiple endothelial cell types, including arterial and venous cells, within a single arterial-venous-like network. Altogether, this strategy enables the fabrication of multi-cellular engineered vasculature with enhanced geometric complexity and phenotypic heterogeneity.

Preeclampsia (PE) is a challenge in maternal healthcare due to its complex nature, characterized by high blood pressure, protein in the urine, and damage to various organs. There is evidence linking PE to endothelial dysfunction (ED), triggered by substances released from an oxygen-deprived placenta. Previous in vitro studies have not considered the impact of in vivo elements, such as the different patterns of blood flow, and laminar (LSS) vs. oscillatory (OSS) shear stress, on the development of ED. We investigated the impact of plasma from healthy pregnant women (HP), subjects with gestational hypertension (GH), and PE patients on global gene expression of human coronary endothelial cells (HCAECs) under LSS and OSS. Our findings revealed a unique transcriptional profile of endothelial cells induced by plasma incubation in LSS. Notably, OSS resulted in similar transcriptomes irrespective of plasma treatment. Under LSS, GH plasma resulted in a proliferative profile, whereas PE plasma was linked to pro-inflammatory and antioxidant profiles compared to HP plasma. Our findings demonstrate that shear stress levels influence the endothelial cell transcriptome in response to plasma from hypertensive pregnancy patients. Both PE and GH can induce endothelial dysfunction under atheroprotective LSS, with a more significant effect observed with PE-derived plasma.

This study aims to explore the causal relationships between serum uric acid level and pulmonary arterial hypertension (PAH) using the Mendelian randomization (MR) approach, and to assess the therapeutic impacts of urate-lowering drugs on PAH. Utilizing published genome-wide association study (GWAS) data, we applied MR and colocalization analysis to assess the link between serum uric acid levesl and PAH across four GWAS datasets from two distinct European populations. The validity and reliability of these findings were confirmed through multiple statistical methods, along with an MR analysis of urate-lowering drug targets to investigate their potential effects on PAH treatment. MR analysis revealed a significant positive correlation between serum uric acid levels and PAH (odds ratio (OR) 1.106, 95% confidence intervals (CI) 1.021-1.200, P = 0.014), corroborated by a replication MR analysis (OR 1.859, 95% CI 1.130-3.057, P = 0.015). No significant heterogeneity or horizontal pleiotropy was found in the sensitivity analyses. However, urate-lowering drugs did not demonstrate a significant direct therapeutic effect on PAH. This study establishes a genetic basis for a causal link between serum uric acid levels and PAH. However, urate-lowering drugs do not appear to have a direct causal effect on improving PAH. These findings provide a novel reference point for developing future therapeutic strategies for PAH.

Cardiovascular diseases, including atherosclerosis, hypertension, and heart failure, remain the leading cause of global mortality, with endothelial dysfunction and vascular remodeling as critical contributors. Integrins, as transmembrane adhesion proteins, are central regulators of cell adhesion, migration, and signaling, playing a pivotal role in maintaining vascular homeostasis and mediating pathological processes such as inflammation, angiogenesis, and extracellular matrix remodeling. This article comprehensively examines the role of integrins in the pathogenesis of cardiovascular diseases, focusing on their dysfunction in endothelial cells and interactions with inflammatory mediators, such as TNF-α. Molecular mechanisms of integrin action are discussed, including their involvement in mechanotransduction, leukocyte adhesion, and signaling pathways that regulate vascular integrity. The review also highlights experimental findings, such as the use of specific integrin-targeting plasmids and immunofluorescence to elucidate integrin functions under inflammatory conditions. Additionally, potential therapeutic strategies are explored, including the development of integrin inhibitors, monoclonal antibodies, and their application in regenerative medicine. These approaches aim not only to mitigate pathological vascular remodeling but also to promote tissue repair and angiogenesis. By bridging insights from molecular studies with their translational potential, this work underscores the promise of integrin-based therapies in advancing the management and treatment of cardiovascular diseases.

Although left ventricular assist devices (LVADs) are an alternative to heart transplantation, their artificial surfaces often lead to serious thrombotic complications requiring high-risk device replacement. Coating blood-contacting surfaces with antithrombogenic endothelial cells is considered an effective strategy for preventing thrombus formation. However, this concept has not yet been successfully implemented in LVADs, as severe cell loss is to be expected, especially on the impeller surface with high prothrombogenic supraphysiological shear stress. This study presents a strategy that exploits the magnetic attraction of the impeller on ECs loaded with iron oxide nanoparticles (IONPs) to minimize shear stress-induced cell detachment from the rotating magnetic impeller while ensuring antithrombogenic EC adhesion, especially as a bridge until they formed their adhesion-promoting matrix. In contrast to polyvinylpyrrolidone (PVP)-coated IONPs, more efficient and safer cell loading is achieved with sodium citrate (Cit)-stabilized IONPs, where incubation with 6.6 µg iron mL-1 Cit-IONPs for 24 h resulting in an average internalization of 23 pg iron per cell. Internalization of Cit-IONP significantly improved cell attraction to the highly magnetic impeller surface without affecting cell viability or antithrombogenic function. This protocol is key for the development of a biohybrid LVAD impeller that can prevent life-threatening thrombosis and hemorrhage in a future clinical application.

This study examines KLF4's role in endothelial cells (ECs), emphasizing its effects on nitric oxide (NO) production, microvascular formation, and oxidative stress regulation following ischemic stroke. Through high-throughput sequencing, we identified eight cell subpopulations in carotid artery tissues post-stroke, with KLF4 notably elevated in ECs. KLF4 overexpression in ECs promoted NO synthesis, enhanced endothelial tube formation, mitigated oxidative stress, and improved smooth muscle cells (SMCs) function, collectively boosting blood flow in ischemic regions. These findings highlight KLF4 as pivotal in vascular regeneration and oxidative stress reduction, positioning it as a promising target for cardiovascular and cerebrovascular therapies.

The blood-brain barrier (BBB) is a highly selective, semipermeable barrier critical for maintaining brain homeostasis. The BBB regulates the transport of essential nutrients, hormones, and signaling molecules between the bloodstream and the central nervous system (CNS), while simultaneously protecting the brain from potentially harmful substances and pathogens. This selective permeability ensures that the brain is nourished and shielded from toxins. An exception to this are brain regions, such as the hypothalamus and circumventricular organs, which are irrigated by fenestrated capillaries, allowing rapid and direct response to various blood components. We overview the metabolic functions of the BBB, with an emphasis on the impact of altered glucose metabolism and insulin signaling on BBB in the pathogenesis of neurodegenerative diseases. Notably, endothelial cells constituting the BBB exhibit distinct metabolic characteristics, primarily generating ATP through aerobic glycolysis. This occurs despite their direct exposure to the abundant oxygen in the bloodstream, which typically supports oxidative phosphorylation. The effects of insulin on astrocytes, which form the glial limitans component of the BBB, show a marked sexual dimorphism. BBB nutrient sensing in the hypothalamus, along with insulin signaling, regulates systemic metabolism. Insulin modifies BBB permeability by regulating the expression of tight junction proteins, angiogenesis, and vascular remodeling, as well as modulating blood flow in the brain. The disruptions in glucose and insulin signaling are particularly evident in neurodegenerative diseases, such as Alzheimer's disease and Parkinson's disease, where BBB breakdown accelerates cognitive decline. This review highlights the critical role of normal glucose metabolism and insulin signaling in maintaining BBB functionality and investigates how disruptions in these pathways contribute to the onset and progression of neurodegenerative diseases.

Cardiovascular and cardiometabolic diseases are leading causes of morbidity and mortality worldwide, driven in part by chronic inflammation. Emerging research suggests that the bone marrow microenvironment, or marrow niche, plays a critical role in both immune system regulation and disease progression. The bone marrow niche is essential for maintaining hematopoietic stem cells (HSCs) and orchestrating hematopoiesis. Under normal conditions, this niche ensures a return to immune homeostasis after acute stress. However, in the setting of inflammatory conditions such as those seen in cardiometabolic diseases, it becomes dysregulated, leading to enhanced myelopoiesis and immune activation. This review explores the reciprocal relationship between the bone marrow niche and cardiometabolic diseases, highlighting how alterations in the niche contribute to disease development and progression. The niche regulates HSCs through complex interactions with stromal cells, endothelial cells, and signaling molecules. However, in the setting of chronic diseases such as hypertension, atherosclerosis, and diabetes, inflammatory signals disrupt the balance between HSC self-renewal and differentiation, promoting the excessive production of proinflammatory myeloid cells that exacerbate the disease. Key mechanisms discussed include the effects of hyperlipidemia, hyperglycemia, and sympathetic nervous system activation on HSC proliferation and differentiation. Furthermore, the review emphasizes the role of epigenetic modifications and metabolic reprogramming in creating trained immunity, a phenomenon whereby HSCs acquire long-term proinflammatory characteristics that sustain disease states. Finally, we explore therapeutic strategies aimed at targeting the bone marrow niche to mitigate chronic inflammation and its sequelae. Novel interventions that modulate hematopoiesis and restore niche homeostasis hold promise for the treatment of cardiometabolic diseases. By interrupting the vicious cycle of inflammation and marrow dysregulation, such therapies may offer new avenues for reducing cardiovascular risk and improving patient outcomes.

This study aimed to investigate the underlying mechanisms involved in the cardioprotective effects of dehydroepiandrosterone (DHEA) on endoplasmic reticulum stress (ERS) -mediated apoptosis in human vascular smooth muscle cells (HVSMCs) and human umbilical vein endothelial cells (HUVECs).

Various concentrations of Dithiothreitol (DTT) were used to induce ERS-mediated apoptosis. DHEA was utilized to inhibit the apoptotic effects of DTT, while estrogen receptor (ER) antagonists ICI 182,780 and G15, the androgen receptor (AR) antagonist flutamide and the aromatase inhibitor letrozole were used to identify the receptors activated during DHEA treatment in HVSMCs and HUVECs. Flow cytometry assessed the apoptotic rate, and Western blotting analysis evaluated the expression levels of ERS-related proteins GRP78 and PERK, and the apoptotic protein marker CHOP. Furthermore, the primary receptor signaling pathways were identified using signaling pathway blockers: LY294002 (PI3K blocker), SP600125 (JNK blocker), and U0126 (ERK1/2 blocker).

In the DTT pretreatment group (0.8 mmol/L, for 8 h), the expressions of GRP78 and CHOP were significantly up regulated, indicating that an optimal ERS model was successfully established. Additionally, 10-4 mmol/L DHEA significantly inhibited the DTT-induced upregulation of GRP78 and CHOP. The results also demonstrated that the apoptotic rate in the DTT group was increased, while DHEA significantly reduced this rate. The addition of ER antagonists ICI 182,780 and G15 to HVSMCs reversed the effects of DHEA; however, the aromatase inhibitor letrozole and the AR antagonist flutamide did not reverse this effect. Notably, the use of the JNK inhibitor SP600125, the PI3K inhibitor LY294002, and the ERK1/2 inhibitor U0126 antagonized the protective effects of DHEA, with SP600125 showing the most significant impact on both HVSMCs and HUVECs.

Our study has identified a novel mechanism underlying the cardioprotective effects of DHEA. Specifically, DHEA may mitigate ERS-induced cell apoptosis by activating estrogen receptors ERα, ERβ, and GPER via the activated JNK pathway.

Ticagrelor has become the standard drug for the treatment of intracranial aneurysms (IAs) with flow diverters (FDs), but the dosage has not been standardized. The effect of platelet function on clinical and imaging prognosis remains unclear. This study aimed to show the effects of different doses of ticagrelor and platelet aggregation function on the clinical and imaging prognosis after FDs treatment of aneurysms. Patients with IAs and underwent FDs stenting were recruited between July 2019 and June 2023. Logistic regression was performed to assess the predictors of incomplete occlusion and in-stent stenosis (ISS). Linear regression analysis, scatter plot and violin diagram were used to investigate the predictors of maximum platelet aggregation rate induced by ADP (ADP-MPA). The study included 156 patients with 206 aneurysms. There was no significant difference in clinical prognosis and aneurysm occlusion rates between the standard-dose group (ticagrelor, 90 mg/bid) and the low-dose group (ticagrelor, 45 mg/bid). Multivariable analysis identified the ADP-MPA ≥ ADP-MPA (median) (24.2%) (p = 0.037) as an independent risk factor for incomplete occlusion of aneurysms. In addition, higher ADP-MPA (p = 0.045) was an independent risk factor for ISS. Uric acid level (p = 0.019) was negatively associated with ADP-MPA, whereas age (p = 0.031) and body mass index (BMI) (p = 0.042) were positively associated with ADP-MPA. The differences of clinical prognosis and aneurysm occlusion rates between the standard-dose group and the low-dose group were not significant for the treatment of aneurysms with FDs. Higher ADP-MPA predicted higher rates of incomplete occlusion and in-stent stenosis. Uric acid level was negatively associated with ADP-MPA, whereas age and BMI were positively associated with ADP-MPA.

Vasoactive molecules are central regulators of vascular tone, angiogenesis and inflammation. Key molecular agents include nitric oxide (NO), endothelin-1 (ET-1), prostacyclin, free triiodothyronine (fT3), leptin, low-density lipoprotein (LDL), high-density lipoprotein (HDL), superoxide dismutase (SOD), and glutathione peroxidase (GPX). Dysregulation of these compounds can lead to endothelial dysfunction, an early predictor of atherosclerosis and cardiovascular diseases (CVD). Maintaining endothelial health is thus essential for vascular homeostasis and cardiovascular risk prevention. Regular exercise serves as a vital protective measure against CVD and the risk of cardiovascular conditions. However, young athletes often significantly exceed recommended levels of training load, engaging in highly intensive training that leads to substantial physiological adaptations. Despite this, research on the impact of exercise on vasoactive substances in children and adolescents, particularly young athletes, is limited and inconsistent. Most studies focus on those with pre-existing conditions, like obesity or diabetes mellitus. Existing findings suggest exercise may favorably affect vascular biomarkers in youth, but methodological variations hinder consistent conclusions. This literature review examines 68 studies on the effects of exercise on vascular molecules in children and adolescents, young athletes, and children and adolescents with pre-existing conditions, offering deeper insights into how exercise may influence vascular health at the molecular level.

Recently, the incidence rate and mortality of various acute or chronic vascular occlusive diseases have increased yearly. As one of the most effective measures to treat them, vascular stents have been widely studied by researchers, and presently, the most commonly used is a drug-eluting stent, which reduces the process of rapid endothelialization because the drug is not selective. Fortunately, with the discovery and exploration of micro-nanostructures that can regulate cells selectively, reducing the incidence of "intravascular restenosis" and achieving rapid endothelialization simultaneously are possible through a special structure that cannot only improve endothelial cells (ECs), but also inhibit smooth muscle cells (SMCs). Therefore, this paper mainly introduces the preparation methods of micro-nanostructures used in the past, as well as the detection methods of EC and SMC. Then, the various functions of different dimensional structures for different cells are summarized and analyzed. Finally, the application of micro-nanostructure in future stent materials is summarized and proposed.

Venous thromboembolism (VTE) and arterial thrombosis (AT) are distinct yet closely related pathological processes. While traditionally considered separate entities, accumulating evidence suggests that they share common risk factors, such as inflammation and endothelial dysfunction (ED). This review explores the parallels and differences between venous and arterial thrombosis, with particular attention to the role of unprovoked VTE and its potential links to atherosclerosis and systemic inflammation. A key focus is the role of ED, which is emerging as a critical factor in thrombogenesis across both the venous and arterial systems. We examine the current methods for clinically detecting ED, including the use of biomarkers and advanced imaging techniques. Additionally, we discuss novel research avenues, such as the potential of endothelial colony-forming cells and other innovative methodologies, to further unravel the complex mechanisms of thrombosis. Finally, we propose future clinical scenarios where targeting endothelial health could pave the way for more effective prevention and treatment strategies in thrombosis management.

Vascular endothelial growth factor receptor inhibitors (VEGFRis) improve cancer patient survival by inhibiting tumor angiogenesis. However, VEGFRis induce treatment-limiting hypertension which has been associated with impaired vascular endothelial cell (EC) function and kidney damage. The mineralocorticoid receptor (MR) regulates blood pressure (BP) via its effects on the vasculature and the kidney. Thus, we interrogated the role of the MR in EC dysfunction, renal impairment, and hypertension in a mouse model of VEGFRi-induced hypertension using sorafenib.

EC dysfunction in mesenteric arterioles was assessed by immunoblotting for phosphorylation of endothelial nitric oxide synthase (eNOS) at serine 1177. Renal damage was measured by assessing glomerular endotheliosis histologically. BP was measured using implanted radiotelemetry.

Six days of sorafenib treatment significantly impaired mesenteric resistance vessel EC function, induced renal damage, and increased BP. Pharmacologic MR blockade with spironolactone prevented the sorafenib-induced decline in eNOS phosphorylation and renal glomerular endotheliosis, without affecting systolic BP (SBP) or diastolic BP. Mice with the MR knocked out specifically in ECs (EC-MR-KO) were protected from sorafenib-induced EC dysfunction and glomerular endotheliosis, whereas smooth muscle cell-specific MR (SMC-MR) knockout mice were not. Neither EC-MR nor SMC-MR knockout affected the degree to which sorafenib increased SBP or diastolic BP.

These results reveal that the MR, specifically in EC but not in SMCs, is necessary for VEGFRi-induced renal and vascular injury. While ineffective at lowering SBP, these data suggest potential therapeutic benefits of MR antagonists, like spironolactone, to protect the vasculature and the kidneys from VEGFRi-induced injury.

Self-propelled micro/nanomotors (MNMs) represent a groundbreaking advancement in precision drug delivery, offering potential solutions to persistent challenges such as systemic toxicity, limited bioavailability, and nonspecific distribution. By transforming various energy sources into mechanical motion, MNMs are able to autonomously navigate through complex physiological environments, facilitating targeted delivery of therapeutic agents to previously inaccessible regions. However, to achieve efficient in vivo drug delivery, biomedical MNMs must demonstrate their ability to overcome crucial physiological barriers encompassing mucosal surfaces, blood flow dynamics, vascular endothelium, and cellular membrane. This review provides a comprehensive overview of the latest strategies developed to address these obstacles while also analyzing the broader challenges and opportunities associated with clinical translation. Our objective is to establish a solid foundation for future research in medical MNMs by focusing on enhancing drug delivery efficiency and advancing precision medicine, ultimately paving the way for practical theragnostic applications and wider clinical adoption.

Pathological vascular remodeling (VR) is characterized by structural and functional alterations in the vascular wall resulting from injury, which significantly contribute to the development of cardiovascular diseases (CVDs). The vascular wall consists primarily of endothelial cells (ECs), vascular smooth muscle cells (VSMCs), and adventitial fibroblasts (AFs), whose interactions are crucial for both the formation of the vascular system and the maintenance of mature blood vessels. Disruptions in the communication between these cell types have been implicated in the progression of VR. This review examines the complex interactions between ECs, VSMCs, and AFs in the context of CVD development, emphasizing a relatively underexplored yet potentially critical mechanism. This interaction framework likely extends to the broader cellular dialogue in the pathogenesis of CVDs, suggesting novel therapeutic strategies for intervention.

The vascular endothelium and its endothelial glycocalyx contribute to the protection of the endothelial cells from exposure to high levels of sodium and help these structures maintain normal function by regulating vascular permeability due to its buffering effect. The endothelial glycocalyx has negative surface charges that bind sodium and limit sodium entry into cells and the interstitial space. High sodium levels can disrupt this barrier and allow the movement of sodium into cells and extravascular fluid. This can generate reactive oxygen species that inhibit nitric oxide production. This leads to vasospasm and increases intravascular pressures. Overtime vascular remodeling occurs, and this changes the anatomy of blood vessels, their intrinsic stiffness, and their response to vasodilators and results in hypertension. Patients with increased salt sensitivity are potentially at more risk for this sequence of events. Studies on the degradation of the glycocalyx provide insight into the pathogenesis of clinical disorders with vascular involvement, but there is limited information available in the context of higher concentrations of sodium. Data on higher intake of sodium and the imbalance between nitric oxide and reactive oxygen species have been obtained in experimental studies and provide insights into possible outcomes in humans. The current western diet with sodium intake above recommended levels has led to the assessment of sodium sensitivity, which has been used in different populations and could become a practical tool to evaluate patients. This would potentially allow more focused recommendations regarding salt intake. This review will consider the structure of the vascular endothelium, its components, the effect of sodium on it, and the use of the salt blood test mini.