Endothelial Transient Receptor Potential Channels and Vascular Remodeling: Extracellular Ca2 + Entry for Angiogenesis, Arteriogenesis and Vasculogenesis

Frontiers in Physiology, Год журнала: 2020, Номер 10

Опубликована: Янв. 21, 2020

Vasculogenesis, angiogenesis and arteriogenesis represent two crucial mechanisms involved in the formation maintenance of vascular network embryonal post-natal life. It has long been known that endothelial Ca2+ signals are key players remodeling; indeed, multiple pro-angiogenic factors, including growth factor, regulate cell fate through an increase intracellular concentration. Transient Receptor Potential (TRP) channel consist a superfamily non-selective cation channels widely expressed within cells. In addition, TRP present main progenitor (EPC) populations, i.e. myeloid angiogenic cells (MACs) colony forming (ECFCs). polymodal can assemble homo- heteromeric complexes may be sensitive to both cues subtle changes local microenvironment. These features render most versatile entry pathway EPCs. Herein, we describe how stimulate remodeling by promoting angiogenesis, vasculogenesis integration environmental, e.g. extracellular factors chemokines, intracellular, reactive oxygen species, decrease Mg2+ levels, or hypercholesterolemia. illustrate induce neovascularization response synthetic agonists small molecule drugs. We focus attention on TRPC1, TRPC3, TRPC4, TRPC5, TRPC6, TRPV1, TRPV4, TRPM2, TRPM4, TRPM7, TRPA1, were shown vasculogenesis. Finally, discuss role aberrant tumor vascularization focusing TRPV2, TRPM8 TRPA1. observations suggest potential therapeutic target disorders featured abnormal vascularization, cancer, ischemic disorders, retinal degeneration neurodegeneration.

Язык: Английский

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TRPV4: A Physio and Pathophysiologically Significant Ion Channel

International Journal of Molecular Sciences, Год журнала: 2020, Номер 21(11), С. 3837 - 3837

Опубликована: Май 28, 2020

Transient Receptor Potential (TRP) channels are a family of ion whose members distributed among all kinds animals, from invertebrates to vertebrates. The importance these molecules is exemplified by the variety physiological roles they play. Perhaps, most extensively studied member this TRPV1 channel; nonetheless, activity TRPV4 has been associated several physio and pathophysiological processes, its dysfunction can lead severe consequences. Several lines evidence derived animal models even clinical trials in humans highlight as therapeutic target protein that will receive more attention near future, be reviewed here.

Язык: Английский

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Riding the tiger – physiological and pathological effects of superoxide and hydrogen peroxide generated in the mitochondrial matrix

Critical Reviews in Biochemistry and Molecular Biology, Год журнала: 2020, Номер 55(6), С. 592 - 661

Опубликована: Ноя. 1, 2020

Elevated mitochondrial matrix superoxide and/or hydrogen peroxide concentrations drive a wide range of physiological responses and pathologies. Concentrations in the are set mainly by rates production, activities dismutase-2 (SOD2) peroxiredoxin-3 (PRDX3), diffusion to cytosol. These considerations can be used generate criteria for assessing whether changes or both necessary sufficient redox signaling pathology: is phenotype affected suppressing production; manipulating levels SOD2, PRDX3 mitochondria-targeted catalase; adding SOD/catalase mimetics antioxidants? Is pathology associated with variants SOD2 genes? Filtering large literature on using these highlights considerable evidence that involved cellular stress management, including apoptosis, autophagy, propagation endoplasmic reticulum stress, senescence, HIF1α signaling, immune responses. They also affect cell proliferation, migration, differentiation, cycle. huge pathologies strong experimental 30-40 may driven peroxide. grouped into overlapping interacting categories: metabolic, cardiovascular, inflammatory, neurological diseases; cancer; ischemia/reperfusion injury; aging its external insults, genetic diseases. Understanding involvement diseases facilitate rational development appropriate therapies.

Язык: Английский

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Caveolar peroxynitrite formation impairs endothelial TRPV4 channels and elevates pulmonary arterial pressure in pulmonary hypertension

Proceedings of the National Academy of Sciences, Год журнала: 2021, Номер 118(17)

Опубликована: Апрель 20, 2021

Recent studies have focused on the contribution of capillary endothelial TRPV4 channels to pulmonary pathologies, including lung edema and injury. However, in hypertension (PH), small arteries are focus pathology, this crucial anatomy remain unexplored PH. Here, we provide evidence that cell caveolae maintain a low arterial pressure under normal conditions. Moreover, activity caveolar is impaired from mouse models PH patients. In PH, up-regulation iNOS NOX1 enzymes at results formation oxidant molecule peroxynitrite. Peroxynitrite, turn, targets structural protein caveolin-1 reduce channels. These suggest caveolin-1-TRPV4 channel signaling lowers pressure, impairment contributes elevated Thus, inhibiting or activity, lowering peroxynitrite levels, may represent strategies for restoring vasodilation

Язык: Английский

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Selenium and Neurological Diseases: Focus on Peripheral Pain and TRP Channels

Current Neuropharmacology, Год журнала: 2020, Номер 18(6), С. 501 - 517

Опубликована: Янв. 6, 2020

Pain is a complex physiological process that includes many components. Growing evidence supports the idea oxidative stress and Ca2+ signaling pathways participate in pain detection by neurons. The main source of endogenous reactive oxygen species (ROS) mitochondrial dysfunction induced membrane depolarization, which turn caused influx into cytosol ROS are controlled antioxidants, including selenium. Selenium plays an important role nervous system, brain, where it acts as cofactor for glutathione peroxidase incorporated selenoproteins involved antioxidant defenses. It has neuroprotective effects through modulation excessive production, inflammation, overload several diseases, inflammatory pain, hypersensitivity, allodynia, diabetic neuropathic nociceptive pain. entry across membranes mediated different channels, transient receptor potential (TRP) some (e.g., TRPA1, TRPM2, TRPV1, TRPV4) can be activated have induction peripheral results recent studies indicate modulator roles selenium inhibition TRP channels dorsal root ganglia experimental animals. This review summarizes protective channel regulation, signaling, apoptosis, induction.

Язык: Английский

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Endothelial TRPV4 channels and vasodilator reactivity

Current topics in membranes, Год журнала: 2020, Номер unknown, С. 89 - 117

Опубликована: Янв. 1, 2020

Язык: Английский

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Reactive Oxygen Species and Endothelial Ca2+ Signaling: Brothers in Arms or Partners in Crime?

International Journal of Molecular Sciences, Год журнала: 2021, Номер 22(18), С. 9821 - 9821

Опубликована: Сен. 10, 2021

An increase in intracellular Ca2+ concentration ([Ca2+]i) controls virtually all endothelial cell functions and is, therefore, crucial to maintain cardiovascular homeostasis. aberrant elevation can indeed lead severe disorders. Likewise, moderate amounts of reactive oxygen species (ROS) induce signals regulate vascular functions, while excessive ROS production may exploit dysregulated dynamics injury. Herein, we survey how and, vice versa, generation the handling machinery promote dysfunction. elicit by regulating inositol-1,4,5-trisphosphate receptors, sarco-endoplasmic reticulum Ca2+-ATPase 2B, two-pore channels, store-operated entry (SOCE), multiple isoforms transient receptor potential (TRP) channels. ROS-induced permeability, angiogenesis, vasorelaxing mediators be exploited therapeutic rescue neurovascular coupling, cancer regression. However, an [Ca2+]i induced formation result dysfunction, inflammatory diseases, metabolic disorders, pulmonary artery hypertension. This information could pave way design alternative treatments interfere with life-threatening interconnection between signaling under pathological conditions.

Язык: Английский

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Role of Transient Receptor Potential Vanilloid 4 in Vascular Function

Frontiers in Molecular Biosciences, Год журнала: 2021, Номер 8

Опубликована: Апрель 26, 2021

Transient receptor potential vanilloid 4 (TRPV4) channels are widely expressed in systemic tissues and can be activated by many stimuli. TRPV4, a Ca 2+ -permeable cation channel, plays an important role the vasculature is implicated regulation of cardiovascular homeostasis processes such as blood pressure, vascular remodeling, pulmonary hypertension edema. Within vasculature, TRPV4 smooth muscle cells, endothelial perivascular nerves. The activation contributes to vasodilation involving nitric oxide, prostacyclin, endothelial-derived hyperpolarizing factor pathways. also directly cause cell hyperpolarization vasodilation. In addition, evoke constriction some specific beds or under pathological conditions. participates control permeability damage, particularly lung capillary barrier injury. It remodeling mainly controlling vasculogenesis arteriogenesis. This review examines function, dilation constriction, permeability, along with possible mechanisms, discusses possibility targeting for therapy.

Язык: Английский

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Pathophysiology and pathogenic mechanisms of pulmonary hypertension: role of membrane receptors, ion channels, and Ca²⁺ signaling

Physiological Reviews, Год журнала: 2022, Номер 103(3), С. 1827 - 1897

Опубликована: Ноя. 24, 2022

The pulmonary circulation is a low-resistance, low-pressure, and high-compliance system that allows the lungs to receive entire cardiac output. Pulmonary arterial pressure function of output vascular resistance, resistance inversely proportional fourth power intraluminal radius artery. Therefore, very small decrease lumen diameter results in significant increase pressure. hypertension fatal progressive disease with poor prognosis. Regardless initial pathogenic triggers, sustained vasoconstriction, concentric remodeling, occlusive intimal lesions, situ thrombosis, wall stiffening are major direct causes for elevated patients other forms precapillary hypertension. In this review, we aim discuss basic principles physiological mechanisms involved regulation lung hemodynamics function, changes vasculature contribute increased pressure, development progression We focus on reviewing roles membrane receptors, ion channels, intracellular Ca

Язык: Английский

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Pathophysiological Roles of the TRPV4 Channel in the Heart

Cells, Год журнала: 2023, Номер 12(12), С. 1654 - 1654

Опубликована: Июнь 17, 2023

The transient receptor potential vanilloid 4 (TRPV4) channel is a non-selective cation that mostly permeable to calcium (Ca2+), which participates in intracellular Ca2+ handling cardiac cells. It widely expressed through the body and activated by large spectrum of physicochemical stimuli, conferring it role variety sensorial physiological functions. Within cardiovascular system, TRPV4 expression reported cardiomyocytes, endothelial cells (ECs) smooth muscle (SMCs), where modulates mitochondrial activity, homeostasis, cardiomyocytes electrical activity contractility, embryonic development fibroblast proliferation, as well vascular permeability, dilatation constriction. On other hand, channels participate several pathological processes such fibrosis, hypertrophy, ischemia-reperfusion injuries, heart failure, myocardial infarction arrhythmia. In this manuscript, we provide an overview implications physiology discuss therapeutic target against diseases.

Язык: Английский

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