Targeted Deletion of Angiotensin II Type 2 Receptor Caused Cardiac Rupture After Acute Myocardial Infarction

Background— Accumulating evidence has suggested that the cardiac renin-angiotensin system is activated during the remodeling process after myocardial infarction (MI). Although 2 types of angiotensin II receptors (AT1 and AT2) are upregulated in the infarcted tissue, the contribution of AT2 to the subsequent fibrogenetic phase of wound healing is less certain. This study was conducted to evaluate the role of AT2 in wound healing after MI using an in vivo intervention study in mice with MI. Methods and Results— We examined myocardial hypertrophy, cardiac fibrosis, and morphological evidence of fibrillar collagen accumulation at the infarcted and noninfarcted regions in male mice lacking the AT2 receptor (Agtr2−/Y) and age-matched wild-type (WT) animals. Of the Agtr2−/Y mice, 63.6% died of cardiac rupture, whereas 23.5% of the WT mice died of the same cause within 1 week. The extent of fibrosis and that of collagen gene expression in Agtr2−/Y mice were significantly reduced compared with WT mice at 1 week af...