Fluvastatin Upregulates the α1C Subunit of CaV1.2 Channel Expression in Vascular Smooth Muscle Cells via RhoA and ERK/p38 MAPK Pathways. (29th December 2014)

• Record Type: Journal Article
• Authors: Ouyang, Qiu-Fang; Han, Ying; Lin, Zhi-Hong; Xie, Hong; Xu, Chang-Sheng; Xie, Liang-Di
• Other Names: Chace Donald H. Academic Editor.
• Is Part Of: Disease markers. Volume 2014(2014)
• Publication Date: 2014-12-29
• Subjects: Diagnosis -- Periodicals; Biochemical markers -- Periodicals; Pathology -- Periodicals; 616
• DOI: 10.1155/2014/237067
• Languages: English
• ISSNs: 0278-0240

Abstract

Abstract : Abnormal phenotypic switch of vascular smooth muscle cell (VSMC) is a hallmark of vascular disorders such as atherosclerosis and restenosis. And this process has been related to remodeling of L-type calcium channel (LTCC). We attempted to investigate whether fluvastatin has any effect on VSMC proliferation and LTCCα 1 C subunit ( L T C C α 1 C ) expression as well as the potential mechanisms involved. The VSMCs proliferation was assayed by osteopontin immunofluorescent staining and [ 3 H]-thymidine incorporation. The cell cycle was detected by flow cytometric analysis. The activity of RhoA was determined with pull-down assay. MAPK activity and L T C C α 1 C expression were assessed by western blotting. We demonstrated fluvastatin prevented the VSMCs dedifferentiating into a proliferative phenotype and induced cell cycle arrest in the G0/G1 phase in response to PDGF-BB stimulation. Fluvastatin dose-dependently reversed the downregulation of L T C C α 1 C expression induced by PDGF-BB. Inhibition of ROCK, ERK, or p38 MAPK activation largely enhanced the upregulation effect of fluvastatin ( P < 0.01 ) . However, blockade of JNK pathway had no effect on L T C C α 1 C expression. We concluded L T C C α 1 C was a VSMC contractile phenotype marker gene. Fluvastatin upregulated L T C C α 1 C expression, at least in part, by inhibiting ROCK, ERK1/2, and p38 MAPK activation. Fluvastatin may be a potential candidate for preventing or treating vascular diseases.