Rho GTPase­activating protein 1 promotes apoptosis of myocardial cells in an ischemic cardiomyopathy model.

ABSTRACT

BACKGROUND: Ischemic cardiomyopathy (ICM) leads to heart failure by causing apoptosis of cardiac myocytes. It is generally believed that a therapy targeting apoptosis of cardiac myocytes would improve the prognosis of patients with ischemic heart disease. AIMS: We aimed to investigate the role of Rho GTPase­activating protein 1 (ARHGAP1) in ICM. METHODS: The cellular model of myocardial ischemia (H9c2 cell model) and a rat model of ICM were established to explore the expression of ARHGAP1. The overexpression of ARHGAP1 was induced in H9c2 myocardial cells to assess protein function. RESULTS: The expression of ARHGAP1 as a result of hypoxic conditions in the cellular and rat models was observed. Its overexpression induced apoptosis of cultured H9c2 cells under normal atmospheric conditions. ARHGAP1 was also shown to initiate the apoptosis pathway by regulating the cell death modulators B­cell lymphoma 2 (Bcl­2) and Bcl­2­associated X protein. CONCLUSIONS: Our results show that the ARHGAP1 expression is closely associated with apoptosis of myocardial cells, which in turn leads to ICM. Thus, ARHGAP1 may become a novel molecular marker of the hypoxia­induced apoptosis pathway and serve as a potential therapeutic target in patients with ICM.