EDN1 and hyperuricemia: In addition, recent studies have shown that hyperuricemia significantly induces cardiomyocyte apoptosis, interstitial fibrosis, diastolic dysfunction and ventricular remodeling through activation of calpain-1 and endoplasmic reticulum (ER) stress (36) or a ROS-dependent endothelin-1 (ET-1) pathway (37), accelerating the occurrence and deterioration of CVD.