Farnesoid X receptor deletion improves cardiac function, structure and remodeling following myocardial infarction in mice

The farnesoid X receptor (FXR) is implicated in cholesterol and bile acid homeostasis; however, its role following myocardial infarction (MI) has yet to be elucidated. The aim of the present study was to investigate the effects of FXR knockout on left ventricular (LV) remodeling following MI. Coronary arteries of wild type (WT) and FXR-/− mice were permanently occluded to cause MI, and serial echocardiographic and histological tests were conducted. At 4 weeks post-MI, FXR-/− mice exhibited significantly smaller infarct sizes (34.20±2.58 vs. 44.20±3.19%), improved ejection fraction (47.31±1.08 vs. 37.64±0.75%) and reduced LV chamber dilation compared with WT mice. LV remodeling was significant as early as 7 days post-MI in FXR-/− compared with WT mice. Histological features associated with enhanced long-term remodeling and improved functionality, such as increased angiogenesis via detection of CD31 and reduced fibrosis, were observed in the FXR-/− group. Myocyte apoptosis within the infarcted zones appeared significantly reduced by day 7 in FXR-/− mice. In conclusion, the results of the present study suggested that FXR knockout may participate in the preservation of post-MI cardiac functionality, via reducing fibrosis and chronic apoptosis, and ameliorating ventricular function.