Improved Recovery After Myocardial Ischemic Infarction by Copper Supplementation

Abstract

Depressed angiogenesis due to ischemic injury leads to myocardial infarction. Copper (Cu) is involved in angiogenesis and ischemia causes copper loss in the heart. The present study was undertaken to test the hypothesis that Cu supplementation improves myocardial angiogenesis, leading to regression of myocardial ischemic infarction in Rhesus monkey model. Coronary artery ligation was used to produce myocardial ischemia and the monkeys developed myocardial infarction 4 weeks after ischemia. A newly developed ultrasound contrast microbubble composed of Cu-albumin coated structure was used to specifically deliver Cu into the infarct area. The treatment was performed twice a week for 4 weeks. This procedure effectively increased Cu concentrations in the infarct area and activated the angiogenesis factors including vascular endothelial growth factor (VEGF), VEGF receptor-1 (VEGFR-1), and other relevant factors. Along with these changes, myocardial infarct size was significantly decreased and the density of myocardial microvessels was significantly increased. In addition, cardiac function was significantly recovered, as evidenced by increased ejection fraction (EF) values and decreased end-systolic volume (ESV) measured by echocardiography. This study thus demonstrated that Cu supplementation improved cardiac structural and functional recovery after ischemic infarction. Supported by National Science Foundation of China (81230004 and 81300109).