Fluvastatin Upregulates Theα1csubunit of CaV1.2 Channel Expression in Vascular Smooth Muscle Cells Via RhoA and ERK/p38 MAPK Pathways

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 LTCCα1Csubunit(LTCCα1C)expression as well as the potential mechanisms involved. The VSMCs proliferation was assayed by osteopontin immunofluorescent staining and [3H]-thymidine incorporation. The cell cycle was detected by flow cytometric analysis. The activity of RhoA was determined with pull-down assay. MAPK activity andLTCCα1Cexpression 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 ofLTCCα1Cexpression 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 onLTCCα1Cexpression. We concludedLTCCα1Cwas a VSMC contractile phenotype marker gene. Fluvastatin upregulatedLTCCα1Cexpression, 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.