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Bkaily G, Jacques D. Calcium Homeostasis, Transporters, and Blockers in Health and Diseases of the Cardiovascular System. Int J Mol Sci 2023; 24:ijms24108803. [PMID: 37240147 DOI: 10.3390/ijms24108803] [Citation(s) in RCA: 18] [Impact Index Per Article: 9.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/21/2023] [Revised: 05/06/2023] [Accepted: 05/10/2023] [Indexed: 05/28/2023] Open
Abstract
Calcium is a highly positively charged ionic species. It regulates all cell types' functions and is an important second messenger that controls and triggers several mechanisms, including membrane stabilization, permeability, contraction, secretion, mitosis, intercellular communications, and in the activation of kinases and gene expression. Therefore, controlling calcium transport and its intracellular homeostasis in physiology leads to the healthy functioning of the biological system. However, abnormal extracellular and intracellular calcium homeostasis leads to cardiovascular, skeletal, immune, secretory diseases, and cancer. Therefore, the pharmacological control of calcium influx directly via calcium channels and exchangers and its outflow via calcium pumps and uptake by the ER/SR are crucial in treating calcium transport remodeling in pathology. Here, we mainly focused on selective calcium transporters and blockers in the cardiovascular system.
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Affiliation(s)
- Ghassan Bkaily
- Department of Immunology and Cell Biology, Faculty of Medicine and Health Sciences, Université de Sherbrooke, Sherbrooke, QC J1H 5N4, Canada
| | - Danielle Jacques
- Department of Immunology and Cell Biology, Faculty of Medicine and Health Sciences, Université de Sherbrooke, Sherbrooke, QC J1H 5N4, Canada
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Li MM, Zheng YL, Wang WD, Lin S, Lin HL. Neuropeptide Y: An Update on the Mechanism Underlying Chronic Intermittent Hypoxia-Induced Endothelial Dysfunction. Front Physiol 2021; 12:712281. [PMID: 34512386 PMCID: PMC8430344 DOI: 10.3389/fphys.2021.712281] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/20/2021] [Accepted: 08/02/2021] [Indexed: 12/17/2022] Open
Abstract
Endothelial dysfunction (ED) is a core pathophysiological process. The abnormal response of vascular endothelial (VE) cells to risk factors can lead to systemic consequences. ED caused by intermittent hypoxia (IH) has also been recognized. Neuropeptide Y (NPY) is an important peripheral neurotransmitter that binds to different receptors on endothelial cells, thereby causing ED. Additionally, hypoxia can induce the release of peripheral NPY; however, the involvement of NPY and its receptor in IH-induced ED has not been determined. This review explains the definition of chronic IH and VE function, including the relationship between ED and chronic IH-related vascular diseases. The results showed that that the effect of IH on VE injury is mediated by the VE-barrier structure and endothelial cell dysfunction. These findings offer new ideas for the prevention and treatment of obstructive sleep apnea syndrome and its complications.
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Affiliation(s)
- Mei-Mei Li
- Department of Cardiology, The Second Affiliated Hospital of Fujian Medical University, Quanzhou, China
| | - Yan-Li Zheng
- Department of Cardiology, The Second Affiliated Hospital of Fujian Medical University, Quanzhou, China
| | - Wan-da Wang
- Department of Cardiology, The Second Affiliated Hospital of Fujian Medical University, Quanzhou, China
| | - Shu Lin
- Department of Cardiology, The Second Affiliated Hospital of Fujian Medical University, Quanzhou, China.,Centre of Neurological and Metabolic Research, The Second Affiliated Hospital of Fujian Medical University, Quanzhou, China.,Diabetes and Metabolism Division, Garvan Institute of Medical Research, Sydney, NSW, Australia
| | - Hui-Li Lin
- Department of Cardiology, The Second Affiliated Hospital of Fujian Medical University, Quanzhou, China
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Borovac JA, D'Amario D, Bozic J, Glavas D. Sympathetic nervous system activation and heart failure: Current state of evidence and the pathophysiology in the light of novel biomarkers. World J Cardiol 2020; 12:373-408. [PMID: 32879702 PMCID: PMC7439452 DOI: 10.4330/wjc.v12.i8.373] [Citation(s) in RCA: 74] [Impact Index Per Article: 14.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/21/2020] [Revised: 05/19/2020] [Accepted: 07/19/2020] [Indexed: 02/06/2023] Open
Abstract
Heart failure (HF) is a complex clinical syndrome characterized by the activation of at least several neurohumoral pathways that have a common role in maintaining cardiac output and adequate perfusion pressure of target organs and tissues. The sympathetic nervous system (SNS) is upregulated in HF as evident in dysfunctional baroreceptor and chemoreceptor reflexes, circulating and neuronal catecholamine spillover, attenuated parasympathetic response, and augmented sympathetic outflow to the heart, kidneys and skeletal muscles. When these sympathoexcitatory effects on the cardiovascular system are sustained chronically they initiate the vicious circle of HF progression and become associated with cardiomyocyte apoptosis, maladaptive ventricular and vascular remodeling, arrhythmogenesis, and poor prognosis in patients with HF. These detrimental effects of SNS activity on outcomes in HF warrant adequate diagnostic and treatment modalities. Therefore, this review summarizes basic physiological concepts about the interaction of SNS with the cardiovascular system and highlights key pathophysiological mechanisms of SNS derangement in HF. Finally, special emphasis in this review is placed on the integrative and up-to-date overview of diagnostic modalities such as SNS imaging methods and novel laboratory biomarkers that could aid in the assessment of the degree of SNS activation and provide reliable prognostic information among patients with HF.
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Affiliation(s)
- Josip Anđelo Borovac
- Department of Pathophysiology, University of Split School of Medicine, Split 21000, Croatia
- Working Group on Heart Failure of Croatian Cardiac Society, Zagreb 10000, Croatia
| | - Domenico D'Amario
- Department of Cardiovascular and Thoracic Sciences, IRCCS Fondazione Policlinico A. Gemelli, Universita Cattolica Sacro Cuore, Rome 00168, Italy
| | - Josko Bozic
- Department of Pathophysiology, University of Split School of Medicine, Split 21000, Croatia
| | - Duska Glavas
- Working Group on Heart Failure of Croatian Cardiac Society, Zagreb 10000, Croatia
- Clinic for Cardiovascular Diseases, University Hospital of Split, Split 21000, Croatia
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Chamoun M, Jacques D, Bkaily G. Extracellular and intracellular tumor necrosis factor alpha modulates cytosolic and nuclear calcium in human cardiovascular cells 1. Can J Physiol Pharmacol 2019; 97:820-828. [PMID: 30897335 DOI: 10.1139/cjpp-2019-0070] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/22/2022]
Abstract
Tumor necrosis factor alpha (TNFα) and its type 1 receptor (TNFR1) are implicated in several autoimmune diseases, including rheumatoid arthritis, and are associated with complications at the cardiovascular level. Using human cardiomyocytes, vascular smooth muscle, vascular endothelial, and endocardial endothelial cells coupled to indirect immunofluorescence, our results showed the presence of TNFR1 at the levels of the plasma membrane (including the cytosol) and mostly at the level of the nuclear membranes (including the nucleoplasm). The distribution of the receptor is different between cell types; however, the density is significantly higher at the nuclear level in all 4 cell types. The density of the receptor was the highest in contractile cells including the cardiomyocytes and vascular smooth muscle cells, compared with endothelial cells including endocardial endothelial and vascular endothelial cells. Using the Ca2+ probe Fluo-3 coupled to quantitative confocal microscopy, our results showed that the cytokine induced a sustained Ca2+ increase in both the cytosol and nucleoplasm of all 4 cell types. This increase was more significant at the nuclear level, mainly in endothelial cells. Our results demonstrated the presence of TNFR1 at both the cell and nuclear membranes of cardiovascular cells, and that its activation modulated both cytosolic and nuclear Ca2+.
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Affiliation(s)
- Marc Chamoun
- Department of Anatomy and Cell Biology, Faculty of Medicine, University of Sherbrooke, Sherbrooke, QC J1H 5N4, Canada.,Department of Anatomy and Cell Biology, Faculty of Medicine, University of Sherbrooke, Sherbrooke, QC J1H 5N4, Canada
| | - Danielle Jacques
- Department of Anatomy and Cell Biology, Faculty of Medicine, University of Sherbrooke, Sherbrooke, QC J1H 5N4, Canada
| | - Ghassan Bkaily
- Department of Anatomy and Cell Biology, Faculty of Medicine, University of Sherbrooke, Sherbrooke, QC J1H 5N4, Canada
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Meng F, Han J, Wang J, Zhang H, Xu C, Meng X. The gender-specific expression of neuropeptide Y and neuropeptide Y receptors in human atrial tissue during cardiopulmonary bypass surgery. J Thorac Dis 2019; 10:6563-6568. [PMID: 30746201 DOI: 10.21037/jtd.2018.11.126] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/06/2022]
Abstract
Background Cardiac sympathetic nervous system is usually activated in cardiopulmonary bypass (CPB) surgery, accompanied by excessive release of norepinephrine (NE). Neuropeptide Y (NPY) has been shown to regulate NE release in the terminal of sympathetic fiber, which is a target for regulating heart function. The expression of NPY and NPY receptor (NPYR) genes in the human atrial tissues during CPB in cardiac surgery was investigated in the present study. Methods A few discarded atrial tissues before and after CPB were collected in 22 patients with rheumatic cardiac valve diseases. The transcriptional levels of NPY and NPYRs were monitored by real-time quantitative polymerase chain reaction (RT-qPCR) method. Moreover, the correlation between the mRNA levels of NPY/NPYRs and the clinical data were investigated in detail. Results The mRNA levels of NPY Y1 and NPY Y5 genes were statistically attenuated in male patients after CPB. Conversely, the expression of NPY, NPY Y1 and NPY Y5 genes were enhanced in female patients. Correlation analysis suggested that there was a significant negative correlation between cardiac ejection fraction (EF) after CPB with the atrial transcriptional level of NPY in male patients. Conclusions These results suggested that the expression of NPY/NPYRs in human atrial tissue during CPB was gender specific and activated NPY signaling was only identified in female patients. The elevated expression level of NPY in male patients was correlated with lower cardiac EF after CPB.
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Affiliation(s)
- Fei Meng
- Cardiac Valve Center, Department of Cardiac Surgery, Beijing Anzhen Hospital, Capital Medical University, Beijing Institute of Heart Lung and Blood Vessel Diseases, Beijing 100029, China
| | - Jie Han
- Cardiac Valve Center, Department of Cardiac Surgery, Beijing Anzhen Hospital, Capital Medical University, Beijing Institute of Heart Lung and Blood Vessel Diseases, Beijing 100029, China
| | - Jiangang Wang
- Cardiac Valve Center, Department of Cardiac Surgery, Beijing Anzhen Hospital, Capital Medical University, Beijing Institute of Heart Lung and Blood Vessel Diseases, Beijing 100029, China
| | - Haibo Zhang
- Cardiac Valve Center, Department of Cardiac Surgery, Beijing Anzhen Hospital, Capital Medical University, Beijing Institute of Heart Lung and Blood Vessel Diseases, Beijing 100029, China
| | - Chunlei Xu
- Cardiac Valve Center, Department of Cardiac Surgery, Beijing Anzhen Hospital, Capital Medical University, Beijing Institute of Heart Lung and Blood Vessel Diseases, Beijing 100029, China
| | - Xu Meng
- Cardiac Valve Center, Department of Cardiac Surgery, Beijing Anzhen Hospital, Capital Medical University, Beijing Institute of Heart Lung and Blood Vessel Diseases, Beijing 100029, China
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Jacques D, Provost C, Normand A, Abou Abdallah N, Al-Khoury J, Bkaily G. Angiotensin II induces apoptosis of human right and left ventricular endocardial endothelial cells by activating the AT 2 receptor 1. Can J Physiol Pharmacol 2019; 97:581-588. [PMID: 30730762 DOI: 10.1139/cjpp-2018-0592] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/19/2022]
Abstract
Endocardial endothelial cells (EECs) form a monolayer lining the ventricular cavities. Studies from our laboratory and the literature have shown differences between EECs isolated from the right and left ventricles (EECRs and EECLs, respectively). Angiotensin II (Ang II) was shown to induce apoptosis of different cell types mainly via AT1 receptor activation. In this study, we verified whether Ang II induces apoptosis of human EECRs and EECLs (hEECRs and hEECLs, respectively) and via which type of receptor. Using the annexin V labeling and in situ TUNEL assays, our results showed that Ang II induced apoptosis of both hEECRs and hEECLs in a concentration-dependent manner. Our results using specific AT1 and AT2 receptor antagonists showed that the Ang-II-induced apoptosis in both hEECRs and hEECLs is mediated mainly via the AT2 receptor. However, AT1 receptor blockade partially prevented Ang-II-induced apoptosis, particularly in hEECRs. Hence, our results suggest that mainly AT2 receptors mediate Ang-II-induced apoptosis of hEECRs and hEECLs. The damage of EECs would affect their function as a physical barrier between the blood and cardiomyocytes, thus affecting cardiomyocyte functions.
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Affiliation(s)
- Danielle Jacques
- Department of Anatomy and Cell Biology, Faculty of Medicine, University of Sherbrooke, Sherbrooke, QC J1H 5N4, Canada
| | - Chantale Provost
- Department of Anatomy and Cell Biology, Faculty of Medicine, University of Sherbrooke, Sherbrooke, QC J1H 5N4, Canada.,Department of Anatomy and Cell Biology, Faculty of Medicine, University of Sherbrooke, Sherbrooke, QC J1H 5N4, Canada
| | - Alexandre Normand
- Department of Anatomy and Cell Biology, Faculty of Medicine, University of Sherbrooke, Sherbrooke, QC J1H 5N4, Canada.,Department of Anatomy and Cell Biology, Faculty of Medicine, University of Sherbrooke, Sherbrooke, QC J1H 5N4, Canada
| | - Nadia Abou Abdallah
- Department of Anatomy and Cell Biology, Faculty of Medicine, University of Sherbrooke, Sherbrooke, QC J1H 5N4, Canada.,Department of Anatomy and Cell Biology, Faculty of Medicine, University of Sherbrooke, Sherbrooke, QC J1H 5N4, Canada
| | - Johny Al-Khoury
- Department of Anatomy and Cell Biology, Faculty of Medicine, University of Sherbrooke, Sherbrooke, QC J1H 5N4, Canada.,Department of Anatomy and Cell Biology, Faculty of Medicine, University of Sherbrooke, Sherbrooke, QC J1H 5N4, Canada
| | - Ghassan Bkaily
- Department of Anatomy and Cell Biology, Faculty of Medicine, University of Sherbrooke, Sherbrooke, QC J1H 5N4, Canada
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Jacques D, Bkaily G. Endocardial endothelial cell hypertrophy takes place during the development of hereditary cardiomyopathy. Mol Cell Biochem 2018; 453:157-161. [DOI: 10.1007/s11010-018-3440-7] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/19/2018] [Accepted: 08/24/2018] [Indexed: 12/16/2022]
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