Liver X Receptor Alpha Is Targeted By Microrna-1 To Inhibit Cardiomyocyte Apoptosis Through A Ros-Mediated Mitochondrial Pathway

Diabetic cardiomyopathy (DCM) is defined as ventricular dysfunction occurring independently of a recognized cause such as hypertension or coronary artery disease. Liver X receptor a (LXR alpha), a subtype of ligand-activated transcription factors LXR alpha, has been considered as a potential pharmacological target in the pathogenesis of cardiovascular and metabolic diseases. However, the potential mechanism of how LXR alpha is regulated in card iomyocytes is still unclear. This study investigated the effect of activating LXR alpha with GW3965 on cardiomyocyte apoptosis and its upstream regulator in glucose-induced H9C2 cells. Our data indicated that GW3965 up-regulated the expression of LXR alpha, inhibited cardiomyocyte apoptosis, and altered the apoptosis-related proteins in glucose-induced H9C2 cells. In addition, GW3965 restored the mitochondrial membrane potential level and decreased the ROS production induced by glucose. Moreover, LXR alpha was confirmed as a direct target of microRNA-1(miR-1) that was involved in cardiomyocyte apoptosis of DCM, and overexpression of miR-1 abrogated the inhibiting effect of GW3965 on glucose-induced apoptosis in H9C2 cells. This study highlights an important role of LXR alpha in the development of DCM and brings new insights into the complex mechanisms involved in the pathogenesis of DCM.