gms | German Medical Science

A number of studies have suggested that the AT2 receptor mediates apoptotic effects in vitro. We have previously provided evidence that both AT1 and AT2 receptors are expressed in adult rat cardiomyocytes, constitutively as well as after myocardial infarction-induced cardiac injury. However, it is currently unknown as to whether angiotensin receptors mediate apoptosis in cardiomyocytes in vivo. We have assessed the regulation of AT1 and AT2 receptors in association with the expression of apoptosis markers such as p53, Bax and caspase-3 at 1 day, 3 days, 7 days and 14 days after experimental MI in rats by Western Blot and/or immunohistochemistry. In addition, the colocalization of angiotensin receptors and apoptosis or cardiomyocyte markers was evaluated by immunofluorescence double labeling. We detected a marked upregulation of cardiac AT1 and AT2 receptors as well as p53 protein on day 7 after experimental MI. Immunohistochemical staining revealed abundant and heterogeneous distribution of p53, Bax and caspase-3 in the myocardium. The strongest staining of p53 was observed on injured cardiomyocytes in the border-zones of the infarction. By contrast, Bax and caspase-3 were mainly located in the area between the border-zone and necrotic lesion and the area surrounding the necrotic lesion, respectively. Immunofluorescence double labeling demonstrated a colocalization of p53 protein and AT1 receptor on injured cardiomyocytes in the border-zone of the infarction. These results indicate that overexpressed AT1 receptors may participate in triggering cardiomyocyte apoptosis by inducing p53-mediated apoptotic cascade after experimental MI.