title: Valsartan inhibits angiotensin II-induced proliferation of vascular smooth muscle cells via regulating the expression of mitofusin 2.
abstract: Angiotensin II (ANGII) plays an important role in the pathogenesis of atherosclerosis by inducing proliferation of vascular smooth muscle cells (VSMCs). In our study, we observed the effects of valsartan on proliferation of cultured VSMCs treated with or without ANGII by cell counting and methyl thiazolyl tetrazolium (MTT) assay, and detected the expression of mitofusin 2 (Mfn2), a newly discovered cell proliferation inhibitor and a related cell proliferation signaling pathway protein by Western blotting. ANGII at a concentration of 10(-6) mol/L significantly stimulated VSMCs proliferation, down-regulated the expression of Mfn2 and up-regulated the expression of Raf and ERK1/2. Valsartan inhibited such effects of ANGII at concentrations of 10(-5) and 10(-6) mol/L, but not at 10(-7) mol/L. Valsartan had no significant effect on the proliferation of untreated VSMCs. These results suggest that valsartan inhibits ANGII-induced proliferation of VSMCs in vitro via Mfn2-Ras-Raf-ERK/MAPK signaling pathway.
authors.affiliation: Department of Cardiology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China.|Department of Cardiology, the Central Hospital of Wuhan, Wuhan, 430014, China.
authors.forename: Hua
authors.initials: H
authors.lastname: Liao
authors.affiliation: Department of Cardiology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China.
authors.forename: Junrong
authors.initials: J
authors.lastname: Gong
authors.affiliation: Department of Cardiology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China.
authors.forename: Wenjuan
authors.initials: W
authors.lastname: Zhang
authors.affiliation: Department of Cardiology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China. xmguo@tjh.tjmu.edu.cn.
authors.forename: Xiaomei
authors.initials: X
authors.lastname: Guo
mesh_terms: D000804:Angiotensin II / Q000008:administration & dosage*; D047228:Angiotensin II Type 1 Receptor Blockers / Q000008:administration & dosage; D000818:Animals; D049109:Cell Proliferation / Q000187:drug effects*; D002478:Cells, Cultured; D004347:Drug Interactions; D020558:GTP Phosphohydrolases; D005786:Gene Expression Regulation / Q000187:drug effects / Q000502:physiology; D020935:MAP Kinase Signaling System / Q000187:drug effects / Q000502:physiology*; D008297:Male; D008565:Membrane Proteins / Q000378:metabolism*; D024101:Mitochondrial Proteins / Q000378:metabolism*; D009131:Muscle, Smooth, Vascular / Q000166:cytology / Q000187:drug effects / Q000502:physiology*; D032389:Myocytes, Smooth Muscle / Q000166:cytology / Q000187:drug effects / Q000502:physiology*; D051381:Rats; D011921:Rats, Inbred WKY; D013777:Tetrazoles / Q000008:administration & dosage*; D014633:Valine / Q000008:administration & dosage / Q000031:analogs & derivatives*; D000068756:Valsartan
chemical_list: D047228:Angiotensin II Type 1 Receptor Blockers; D008565:Membrane Proteins; D024101:Mitochondrial Proteins; D013777:Tetrazoles; D000804:Angiotensin II; D000068756:Valsartan; D020558:GTP Phosphohydrolases; C489710:Mfn2 protein, rat; D014633:Valine