Evidence of a role for TRPC channels in VEGF-mediated increased vascular permeability in vivo

Abstract

Pocock, T. M., R. R. Foster, and D. O. Bates. Evidence of a role for TRPC channels in VEGF-mediated increased vascular permeability in vivo.

Elucidation of a TRPC6-TRPC5 Channel Cascade That Restricts Endothelial Cell Movement

“…TRPC5 and TRPC6 are externalized in the plasma membrane with subsequent increased [Ca 2ϩ ] i and disruption of EC migration. TRPC6 is involved in vascular endothelial growth factor-mediated increase in vascular permeability and in EC contraction in response to thrombin (Pocock et al, 2004;Singh et al, 2007), but other functions of TRPC5 and TRPC6 in ECs are largely unknown. The role of TRPC5 or TRPC6 in the regulation of EC migration has not Ϫ/Ϫ mice were incubated with lysoPC for 1 h. Cell surface proteins were biotinylated, and immunoblot analysis was performed for biotinylated TRPC5 (top panel).…”

“…LysoPC activated TRPC5 channels in HEK cells overexpressing TRPC5 (Flemming et al, 2006) and increased [Ca 2ϩ ] i in smooth muscle cells that have endogenous TRPC6 channels (So et al, 2005). Because TRPC5 and TRPC6 are expressed in bovine ECs (Yip et al, 2004) and can be store-independent (Nilius and Droogmans, 2003;Zeng et al, 2004) and because TRPC6 plays a role in vascular endothelial growth factor-mediated microvessel permeability and thrombin-induced EC shape change (Pocock et al, 2004;Singh et al, 2007), we explored This article was published online ahead of print in MBC in Press (http://www.molbiolcell.org/cgi/doi/10.1091/mbc.E07-08 -0765) on May 21, 2008. the role of TRPC5 and TRPC6 in lysoPC-induced calcium influx and subsequent inhibition of EC migration.…”

Regulation of TRPM2 channels in neutrophil granulocytes by ADP-ribose: a promising pharmacological target

“…For example, the non-steroidal antiinflammatory compound flufenamic acid (FFA) has been described as an inhibitor of the channel TRPM2 . In the literature, many other effects have been attributed to FFA including block (Tesfai et al 2001;Lee et al 2003b;Guinamard et al 2004) or even stimulation of some TRP channels (Inoue et al 2001;Pocock et al 2004). Further targets of fenamates like FFA include chloride channels (Kim et al 2003), voltage gated Na + and K + channels (Lee and Wang 1999) and GABA A receptors (Sinkkonen et al 2003); in part the effective concentrations were similar as on TRPM2.…”

Functional properties of ion channels and transporters in tumour vascularization

“…VEGF mediates NSOCE through TRPC6 in human microvascular EC [60,82]. Dominant negative TRPC6 significantly reduces EC number, migration, tubulogenesis and sprouting [31,44].…”

“…HMEC, human microvascular EC; HPAEC, human pulmonary artery EC; HUVEC, human umbilical vein EC; EA.hy926, EC line derived from HUVEC fused with human lung adenocarcinoma cell line A549; PAEC, porcine aortic endothelial cells; BTEC, tumour-derived EC from breast carcinoma; H5VEC, heart endothelioma (H5V) EC; MAEC, mouse aortic EC; EPC, endothelial progenitor cells; RCC-EPC, EPC isolated from renal carcinoma patients; Numbers in parenthesis indicate the respective reference number. EPC [30] HMEC [31] BTEC [32] RCC-EPC [29] HUVEC [33 -35] HUVEC [36] HUVEC [37] HUVEC [38] HUVEC [36,39] MAEC from KO mice [40] HMEC [41,42] EPC [43] survival and proliferation RCC-EPC [29] EPC [30] HMEC [31] HUVEC [44] PAEC [45] H5V EC [46] HUVEC [40] HUVEC, HMEC [41,55] EPC [43] permeability HMEC,HUVEC [56 -58] HPAEC [59] Frog mesenteric microvessels [60] H5V EC [46] HUVEC [61] in vivo angiogenesis zebrafish [62] CAM [44] collateral growth [45] HERG-1-Retinoblastoma [63] EAG1-Xenograft in SCID mice and human osteosarcoma [27,28] CAM [54] xenograft in nude mice [38] Rabbit cornea [64] human mammary carcinoma, glioblastoma [65,66] AQP1 KO mice and C57BL/ 6 mice …”