TRP channels in endothelial function and dysfunction.
Endothelial cells produce various factors that regulate vascular tone, vascular permeability, angiogenesis, and inflammatory responses. The dysfunction of endothelial cells is believed to be the major culprit in various cardiovascular diseases, including hypertension, atherosclerosis, heart and renal failure, coronary syndrome, thrombosis, and diabetes. Endothelial cells express multiple transient receptor potential (TRP) channel isoforms, the activity of which serves to modulate cytosolic Ca(2+) levels ([Ca(2+)](i)) and regulate membrane potential, both of which affect various physiological processes. The malfunction and dysregulation of TRP channels is associated with endothelial dysfunction, which is reflected by decreased nitric oxide (NO) bioavailability, inappropriate regulation of vascular smooth muscle tonicity, endothelial barrier dysfunction, increased oxidative damage, impaired anti-thrombogenic properties, and perturbed angiogenic competence. Evidence suggests that dysregulation of TRPC4 and -C1 results in vascular endothelial barrier dysfunction; malfunction of TRPP1 and -P2 impairs endothelial NO synthase; the reduced expression or activity of TRPC4 and -V1 impairs agonist-induced vascular relaxation; the decreased activity of TRPV4 reduces flow-induced vascular responses; and the activity of TRPC3 and -C4 is associated with oxidative stress-induced endothelial damage. In this review, we present a comprehensive summary of the literature on the role of TRP channels in endothelial cells, with an emphasis on endothelial dysfunction.
Kwan
Hiu-Yee
HY
Li Ka Shing Institute of Health Sciences, Faculty of Medicine, Chinese University of Hong Kong, Hong Kong, China.
Huang
Yu
Y
Yao
Xiaoqiang
X
D000818:Animals; D002199:Capillary Permeability / Q000502:physiology; D002318:Cardiovascular Diseases / Q000209:etiology / Q000473:pathology / Q000503:physiopathology*; D042783:Endothelial Cells / Q000473:pathology* / Q000502:physiology*; D006801:Humans; D008954:Models, Biological; D009389:Neovascularization, Pathologic / Q000209:etiology; D018384:Oxidative Stress / Q000502:physiology; D013314:Stress, Mechanical; D050051:Transient Receptor Potential Channels / Q000502:physiology*
D050051:Transient Receptor Potential Channels