title: Static pressure drives proliferation of vascular smooth muscle cells via caveolin-1/ERK1/2 pathway.
abstract: Intimal hyperplasia plays an important role in various types of vascular remodeling. Mechanical forces derived from blood flow are associated with the proliferation of vascular smooth muscle cells (VSMC). This contributes to many vascular disorders such as hypertension, atherosclerosis and restenosis after percutaneous transluminal angioplasty (PTA). In this study, we show that static pressure induces the proliferation of VSMC and activates its related signal pathway. VSMC from a rat aorta were treated with different pressures (0, 60, 90, 120, 150 and 180 mm Hg) in a custom-made pressure incubator for 24h. The most active proliferation of VSMC was detected at a pressure of 120 mm Hg. VSMC was also incubated under a static pressure of 120 mm Hg for different time intervals (0, 2, 4, 8, 12 and 24h). We found that static pressure significantly stimulates VSMC proliferation. Extracellular signal-regulated kinases 1/2 (ERK1/2) activation showed a peak at the pressure of 120 mm Hg at 4-h time point. Moreover, caveolin-1 expression was significantly inhibited by rising static pressure. Downregulation of VSMC proliferation could be found after PD98059 (ERK1/2 phosphorylation inhibitor) treatment. Our data also showed that a siRNA-mediated caveolin-1 knock down increased ERK1/2 phosphorylation and VSMC proliferation. These results demonstrate that static pressure promotes VSMC proliferation via the Caveolin-1/ERK1/2 pathway.
authors.affiliation: Division of Pharmacoproteomics, Institute of Pharmacy and Pharmacology, Research Center of Life Science, University of South China, Hengyang, Hunan 421001, China. luodixian_2@163.com
authors.forename: Di-xian
authors.initials: DX
authors.lastname: Luo
authors.forename: Jiming
authors.initials: J
authors.lastname: Cheng
authors.forename: Yan
authors.initials: Y
authors.lastname: Xiong
authors.forename: Junmo
authors.initials: J
authors.lastname: Li
authors.forename: Chenglai
authors.initials: C
authors.lastname: Xia
authors.forename: Canxin
authors.initials: C
authors.lastname: Xu
authors.forename: Chun
authors.initials: C
authors.lastname: Wang
authors.forename: Bingyang
authors.initials: B
authors.lastname: Zhu
authors.forename: Zhuowei
authors.initials: Z
authors.lastname: Hu
authors.forename: Duan-fang
authors.initials: DF
authors.lastname: Liao
mesh_terms: D000818:Animals; D001011:Aorta; D051242:Caveolin 1 / Q000235:genetics / Q000378:metabolism*; D049109:Cell Proliferation; D005419:Flavonoids / Q000494:pharmacology; D019950:Mitogen-Activated Protein Kinase 1 / Q000378:metabolism*; D048052:Mitogen-Activated Protein Kinase 3 / Q000378:metabolism*; D009131:Muscle, Smooth, Vascular / Q000378:metabolism / Q000502:physiology*; D032389:Myocytes, Smooth Muscle / Q000378:metabolism / Q000502:physiology*; D011312:Pressure; D047428:Protein Kinase Inhibitors / Q000494:pharmacology; D051381:Rats
chemical_list: C495537:Cav1 protein, rat; D051242:Caveolin 1; D005419:Flavonoids; D047428:Protein Kinase Inhibitors; C535149:Mapk1 protein, rat; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3; C093973:2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one