C-reactive protein induces p53-mediated cell cycle arrest in H9c2 cardiac myocyte

Abstract

C-reactive protein (CRP) is one of the most important biomarkers for cardiovascular diseases. Recent studies have shown that CRP regulates cell survival, differentiation, and hypoxia-induced apoptosis. However, the effect of CRP on cell cycle has not been studied yet. Therefore, our study investigated whether CRP would regulate cell cycle progression in H9c2 cardiac myocytes.CRP (10-3 ~ 50 μg/ml) inhibited the proliferation of H9c2 cardiac myocytes dose dependently. Apoptotic analysis demonstrated no effect of CRP on apoptosis of H9c2 cardiac myocytes. However, flow cytometry analysis showed that CRP-treated H9c2 cardiac myocytes displayed cell cycle arrest in G0/G1 phase. CRP reduced cell cycle related proteins such as, cdk4 and cdk6, as well as resulted in increased p53 phosphorylation and p21. CRP-induced activation of p53 was reduced by extracellular signal-regulated kinase (ERK) inhibitor, U0126 and CRP also activated ERK activity. We demonstrated that H9c2 cardiac myocytes highly expressed high amount of FcγRIIIa receptor with activation after CRP treatment. Silencing FcγRIIIa receptor by siRNA suppressed CRP-mediated ERK, p53, p21 activation and resulted in normalization of cdk6 expression. These results suggest that activation of ERK and p53 are involved in CRP-mediated H9c2 cardiac myocytes cell cycle arrest via FcγRIIIa receptor. Our findings implicate potential effect of CRP on cardiac myocyte survival in cardiovascular diseases.