Rosuvastatin inhibits the smooth muscle cell proliferation by targeting TNF? mediated Rho kinase pathway.

ABSTRACT: OBJECTIVE: To investigate whether Tumor Necrosis Factor-alpha (TNF?) is capable of activating Rho kinase pathway which leads to smooth muscle cell proliferation and the intervention function of Rosuvastatin, and clarify the mechanism and intervention manner of anti-atherosclerosis by Rosuvastatin. METHODS: Wistar neonate rat smooth muscle cells were cultured, and the activity of cell proliferation was determined by methyl thiazolyl tetrazolium (MTT). The expression of Rho kinase genes after the stimulation of TNF? was evaluated by RT-PCR. Western blot method was used to measure the protein expression of proliferating cell nuclear antigen (PCNA) after TNF? stimulation and Rosuvastatin intervention in smooth muscle cell. RESULTS: The TNF? stimulation significantly enhanced the expression of Rho kinase and increased the expression of PCNA protein in smooth muscle cells (P < 0.05). These effects were positively correlated with prolonged treatment whereas additional Rosuvastatin administration inhibited the above-mentioned effects (P < 0.05). CONCLUSIONS: The activation of TNF? mediated Rho kinase signaling pathway can significantly promote smooth muscle cell proliferation, and Rosuvastatin can not only inhibit this pathway but also the induced proliferation.

SUBMITTER: Sun X 

PROVIDER: S-EPMC3418909 | biostudies-other | 2012 Jun

REPOSITORIES: biostudies-other