Recent developments in vascular endothelial cell transient receptor potential channels.
Among the 28 identified and unique mammalian TRP (transient receptor potential) channel isoforms, at least 19 are expressed in vascular endothelial cells. These channels appear to participate in a diverse range of vascular functions, including control of vascular tone, regulation of vascular permeability, mechanosensing, secretion, angiogenesis, endothelial cell proliferation, and endothelial cell apoptosis and death. Malfunction of these channels may result in disorders of the human cardiovascular system. All TRP channels, except for TRPM4 and TRPM5, are cation channels that allow Ca2+ influx. However, there is a daunting diversity in the mode of activation and regulation in each case. Specific TRP channels may be activated by different stimuli such as vasoactive agents, oxidative stress, mechanical stimuli, and heat. TRP channels may then transform these stimuli into changes in the cytosolic Ca2+, which are eventually coupled to various vascular responses. Evidence has been provided to suggest the involvement of at least the following TRP channels in vascular function: TRPC1, TRPC4, TRPC6, and TRPV1 in the control of vascular permeability; TRPC4, TRPV1, and TRPV4 in the regulation of vascular tone; TRPC4 in hypoxia-induced vascular remodeling; and TRPC3, TRPC4, and TRPM2 in oxidative stress-induced responses. However, in spite of the large body of data available, the functional role of many endothelial TRP channels is still poorly understood. Elucidating the mechanisms regulating the different endothelial TRP channels, and the associated development of drugs selectively to target the different isoforms, as a means to treat cardiovascular disease should, therefore, be a high priority.
Yao
Xiaoqiang
X
Department of Physiology, Chinese University of Hong Kong, China. yao2068@cuhk.edu.hk
Garland
Christopher J
CJ
D000818:Animals; D002118:Calcium / Q000378:metabolism; D015220:Calcium Channels / Q000502:physiology; D002199:Capillary Permeability; D021941:Caveolae / Q000502:physiology; D042783:Endothelial Cells / Q000737:chemistry / Q000502:physiology*; D006801:Humans; D008565:Membrane Proteins / Q000502:physiology; D018919:Neovascularization, Physiologic; D009419:Nerve Tissue Proteins / Q000502:physiology; D009619:Nociceptors / Q000502:physiology; D018384:Oxidative Stress; D010766:Phosphorylation; D015398:Signal Transduction; D013314:Stress, Mechanical; D000074025:TRPA1 Cation Channel; D050052:TRPC Cation Channels / Q000032:analysis / Q000502:physiology*; D000074287:TRPC6 Cation Channel; D050916:TRPV Cation Channels / Q000502:physiology; D013696:Temperature; D050051:Transient Receptor Potential Channels / Q000032:analysis / Q000502:physiology*
D015220:Calcium Channels; D008565:Membrane Proteins; D009419:Nerve Tissue Proteins; D000074025:TRPA1 Cation Channel; C473350:TRPA1 protein, human; D050052:TRPC Cation Channels; C104603:TRPC3 cation channel; C489571:TRPC4 ion channel; D000074287:TRPC6 Cation Channel; C117032:TRPC6 protein, human; D050916:TRPV Cation Channels; C494482:TRPV1 protein, human; C416986:TRPV4 protein, human; D050051:Transient Receptor Potential Channels; C096351:transient receptor potential cation channel, subfamily C, member 1; D002118:Calcium