Atorvastatin inhibits PDGF-BB induced vascular smooth muscle cells proliferation and migration in cerebrovascular diseases

Backgrounds: Vascular smooth muscle cells (VSMCs) dedifferentiation is known to be critical in the genesis of lots of cerebrovascular diseases like atherosclerosis, intimal hyperplasia, and restenosis. This study aims to verify whether atorvastatin (ATV) inhibits rat brain arterial VSMCs dedifferentiation through down-regulation of kruppel-like transcription factor 4 (KLF4). Material and methods: The primary culture and identification of rat brain arterial VSMCs was conducted and VSMCs in passage 2-8 were used for the following experiments. Platelet derived growth factor-BB (PDGF-BB) was used to induce VSMCs dedifferentiation. KLF4-siRNA or pcDNA3.1+HA-KLF4 were used to suppress or increased the expression of KLF4 in VSMCs respectively. After incubation in different concentrations of ATV, the proliferation and migration ability of the VSMCs were tested by MTT assay, Transwell chambers, and wound healing assay. Immunocytochemistry (ICC) was used to evaluate VSMCs morphology and SM-actin rearrangement. Western blotting was employed to investigate the expressions of SM-actin, calponin, SM-MHC, OPN, KLF4 in VSMCs. Results: PDGF-BB improved the proliferation and migration ability of VSMCs and increased the expressions of calponin, SM-MHC, KLF4. ATV significantly inhibited the induction of these phenotypic changes induced by PDGF-BB. Meanwhile ATV suppressed the expression of KLF4 in the VSMCs. Identical to ATV, down-regulation of KLF4 by KLF-siRNA could also inhibit VSMC dedifferentiation. In addition, up-regulation of KLF4 by pcDNA3.1+HA-KLF4 reversed the ATV-induced inhibition of VSMC dedifferentiation. Conclusion: ATV inhibits PDGF-BB induced VSMCs dedifferentiation by down-regulation of KLF4.