title: Involvement of connexin 43 in angiotensin II-induced migration and proliferation of saphenous vein smooth muscle cells via the MAPK-AP-1 signaling pathway.
abstract: Proliferation and migration of vascular smooth muscle cells (VSMCs) lead to intimal thickening and influence the long-term patency of venous graft post coronary arterial bypass graft. There is increasing evidence that connexins are involved in the development of intimal hyperplasia and restenosis. We assessed connexin 43 (Cx43) expression and its role in angiotensin II-induced proliferation and migration of smooth muscle cells and the signal pathways involved in human saphenous vein bypass conduits. Angiotensin II significantly increased gap junctional intercellular communication and induced the expression of Cx43 in human saphenous vein SMCs in a dose- and time-dependent manner through angiotensin II type 1 receptor. The effect of angiotensin II was blocked by siRNA of ERK 1/2, p38 MAPK and JNK, respectively. Overexpression of Cx43 markedly increased the proliferation of saphenous vein SMCs. However, siRNA for Cx43 inhibited angiotensin II-induced proliferation, cyclin E expression and migration of human saphenous vein SMCs. In dual-luciferase reporter assay, angiotensin II markedly activated AP-1 transcription factor, which was significantly attenuated by a dominant-negative AP-1 (A-Fos) with subsequent inhibition of angiotensin II-induced transcriptional expression of Cx43. These data demonstrate the role of Cx43 in the proliferation and migration of human saphenous vein SMCs and angiotensin II-induced Cx43 expression via mitogen-activated protein kinases (MAPK)-AP-1 signaling pathway.
authors.affiliation: Department of Biomedical Sciences, Creighton University School of Medicine, Omaha, NE 68178, USA.
authors.forename: Guanghong
authors.initials: G
authors.lastname: Jia
authors.forename: Gang
authors.initials: G
authors.lastname: Cheng
authors.forename: Deepak M
authors.initials: DM
authors.lastname: Gangahar
authors.forename: Devendra K
authors.initials: DK
authors.lastname: Agrawal
mesh_terms: D000368:Aged; D000804:Angiotensin II / Q000494:pharmacology*; D002450:Cell Communication / Q000187:drug effects; D002465:Cell Movement / Q000187:drug effects*; D049109:Cell Proliferation / Q000187:drug effects; D018031:Connexin 43 / Q000378:metabolism*; D004789:Enzyme Activation / Q000187:drug effects; D017629:Gap Junctions / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D048031:JNK Mitogen-Activated Protein Kinases / Q000378:metabolism; D020935:MAP Kinase Signaling System / Q000187:drug effects*; D019950:Mitogen-Activated Protein Kinase 1 / Q000378:metabolism; D048052:Mitogen-Activated Protein Kinase 3 / Q000378:metabolism; D032389:Myocytes, Smooth Muscle / Q000166:cytology / Q000187:drug effects / Q000201:enzymology*; D034741:RNA, Small Interfering / Q000378:metabolism; D044140:Receptor, Angiotensin, Type 1 / Q000378:metabolism; D012501:Saphenous Vein / Q000166:cytology* / Q000187:drug effects / Q000201:enzymology; D018808:Transcription Factor AP-1 / Q000378:metabolism*; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism
chemical_list: D018031:Connexin 43; D034741:RNA, Small Interfering; D044140:Receptor, Angiotensin, Type 1; D018808:Transcription Factor AP-1; D000804:Angiotensin II; D048031:JNK Mitogen-Activated Protein Kinases; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3; D048051:p38 Mitogen-Activated Protein Kinases