Expression of p53 in myocardium following coronary microembolization in rats and its significance.

BACKGROUND: Cardiomyocyte apoptosis is a primary cause for coronary microembolization (CME)-induced cardiac dysfunction. p53 induces cell growth retardation and apoptosis through stress pathway. The present study investigated the mechanism of p53-induced myocardial apoptosis and cardiac dysfunction by activating the mitochondrion apoptotic pathway following CME.

METHODS: Forty SD rats were equally divided into microembolization (CME), sham operation (sham), CME+siRNA-p53, and CME+control-p53 groups. The CME rat model was established by injecting microembolization spheres via the left ventricle. Cardiac ultrasound, TUNEL, fluorescence quantitative PCR, and Western blot were used to assess the cardiac function indicators, cardiomyocyte apoptosis, and the expressions of mRNA and protein in myocardial tissues, respectively.

RESULTS: Echocardiography revealed a significantly reduced cardiac function of the CME group than the sham group while the CME-induced cardiac dysfunction was improved in the CME+siRNA-p53 group. The indicators of myocardial apoptosis in the CME group increased significantly than the sham group; those of the CME+siRNA-p53 group decreased significantly than the CME group. Fluorescence quantitative PCR and Western blot demonstrated that p53, Bbc3 (PUMA), and cleaved caspase-3 expressions were significantly increased, and BCL-2 expression was declined in myocardial tissues of the CME group compared to the sham group. A contrasting result was observed in the CME+siRNA-p53 group as compared to the CME group.

CONCLUSIONS: P53 is involved in the CME-induced cardiac dysfunction, which may up-regulate Bbc3 to activate BCL-2/caspase3 mitochondrial apoptotic pathway and induce myocardial apoptosis. Inhibiting the p53 expression can effectively suppress this pathway, thereby reducing myocardial apoptosis and cardiac dysfunction.