title: Role of TRPC1 and NF-kappaB in mediating angiotensin II-induced Ca2+ entry and endothelial hyperpermeability.
abstract: Endothelial dysfunction is associated with cardiovascular diseases. The Ca(2+) influx occurring via activation of plasmalemma Ca(2+) channels was shown to be critical in signaling the increase in endothelial permeability in response to a variety of permeability-increasing mediators. It has been reported that angiotensin II (AngII) could induce Ca(2+) signaling in some cells, and transient receptor potential canonical 1 (TRPC1) had an important role in this process. The objective of this study was to examine the mechanism of AngII-induced Ca(2+) entry and vascular endothelial hyperpermeability. Human umbilical vein endothelial cells (HUVECs) exposed to AngII exhibited dose-dependent increase in [Ca(2+)]i and endothelial permeability. Quantitative real-time RT-PCR and Western blotting showed that the level of TRPC1 expression had increased significantly at 12h and at 24h after treatment of HUEVCs with AngII. The expression of p65 was suppressed using an RNAi strategy. The results showed that the NF-kappaB signaling pathway and type-1 receptor of AngII was involved in AngII-induced TRPC1 upregulation. Moreover, knockdown of TRPC1 and NF-kappaB expression attenuates AngII-induced [Ca(2+)]i and endothelial permeability. NF-kappaB and TRPC1 have critical roles in AngII-induced Ca(2+) entry and endothelial permeability.
authors.affiliation: Department of Cardiology, Kunming General Hospital of Chengdu Military Area, Yunnan 650032, China.
authors.forename: Li-xia
authors.initials: LX
authors.lastname: Yang
authors.forename: Rui-wei
authors.initials: RW
authors.lastname: Guo
authors.forename: Bei
authors.initials: B
authors.lastname: Liu
authors.forename: Xian-mei
authors.initials: XM
authors.lastname: Wang
authors.forename: Feng
authors.initials: F
authors.lastname: Qi
authors.forename: Chuan-ming
authors.initials: CM
authors.lastname: Guo
authors.forename: Yan-kun
authors.initials: YK
authors.lastname: Shi
authors.forename: Hong
authors.initials: H
authors.lastname: Wang
mesh_terms: D000804:Angiotensin II / Q000494:pharmacology*; D015153:Blotting, Western; D002118:Calcium / Q000378:metabolism*; D002463:Cell Membrane Permeability / Q000187:drug effects / Q000235:genetics; D002478:Cells, Cultured; D024202:Electrophoretic Mobility Shift Assay; D042783:Endothelial Cells / Q000187:drug effects* / Q000378:metabolism; D004730:Endothelium, Vascular / Q000166:cytology; D005786:Gene Expression Regulation / Q000187:drug effects*; D055785:Gene Knockdown Techniques; D006801:Humans; D016328:NF-kappa B / Q000235:genetics / Q000378:metabolism*; D034622:RNA Interference; D020133:Reverse Transcriptase Polymerase Chain Reaction; D050052:TRPC Cation Channels / Q000235:genetics / Q000378:metabolism*
chemical_list: D016328:NF-kappa B; D050052:TRPC Cation Channels; C096351:transient receptor potential cation channel, subfamily C, member 1; D000804:Angiotensin II; D002118:Calcium