TRP channels in endothelial function and dysfunction

Abstract

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.

Remodelling of Ca2+transport in cancer: how it contributes to cancer hallmarks?

“…The involvement of diacylaglycerol-gated TRPC3 or TRPC6 was implicated in VEGF-induced permeability of microvascular ECs [98,99]. ECs also express members of TRP family (TRPM and TRPV), as well as STIM and ORAI involved in different aspects of malignant pro-angiogenic behaviours such as EC proliferation, migration and permeability [88,89,97] (figure 4). In addition to directly promoting EC proliferation, migration and permeability, Ca 2þ influx through TRPs might stimulate ECs to produce and release the angiogenic growth factors VEGF, FGF and PDGF, which in turn might stimulate angiogenesis in an autocrine or paracrine manner (figure 4).…”

“…A number of the TRP-channel family members are expressed in ECs contributing the angiogenic process by providing agonist-or mechanical stretch-induced Ca 2þ entry [85,88,97] (figure 4). In particular, TRPC1 and TRPC4 channels, which exhibit a store-dependent mode of gating, have been implicated in Ca 2þ influx required for the pro-angiogenic response of ECs.…”

Update on vascular endothelial Ca2+signalling: A tale of ion channels, pumps and transporters

“…TRP subunits within one subfamily may assemble in either homo-or heterotetramers and this gives rise to large variability in their biophysical properties and activating mechanisms [19,200,201] . Vascular ECs have been shown to express TRP channels from all subfamilies [8,150] . More specifically, all the TRPC, all TRPV, all TRPM except TRPM5, TRPP1, TRPP2 and TRPA1 are present in ECs (Tables 2-4).…”

“…Most, but not all, endothelial SMOCs, as well as MSCs, belong to the TRP family of nonselective cation channels [4,8,19,[148][149][150] , whereas the molecular nature of SOCs is still debated [151,152] . The inrush of Ca 2+ ions consequent to the opening of the Ca 2+ -permeable membrane route is governed by the following equation:…”

Multiple Roles of Protein Kinase A in Arachidonic Acid–Mediated Ca2+ Entry and Tumor-Derived Human Endothelial Cell Migration

“…In addition, it is worth noting that a number of different endothelial calcium-permeable channels are substrates for PKA phosphorylation, including some members of the transient receptor potential (TRP) superfamily of proteins. Interestingly, some of them (including TRPV1 and TRPV4) are also regulated by AA and its metabolites, as well as by NO through S-nitrosylation (23)(24)(25)(26).…”