Acute CD47 Blockade During Ischemic Myocardial Reperfusion Enhances Phagocytosis-Associated Cardiac Repair

Shuang, Zhang, Xin Yi, Yeap, Matthew, DeBerge, Nivedita K., Naresh, Kevin, Wang, Zhengxin, Jiang, Jane E., Wilcox, Steven M., White, John P., Morrow, Paul W., Burridge, Daniel, Procissi, Evan A., Scott, William, Frazier, Edward B., Thorp

JACC: Basic to Translational Science |

Our data suggest that, after a myocardial infarction, integrin-associated protein CD47 on cardiac myocytes is elevated. In culture, increased CD47 on the surface of dying cardiomyocytes impairs phagocytic removal by immune cell macrophages. After myocardial ischemia and reperfusion, acute CD47 inhibition with blocking antibodies enhanced dead myocyte clearance by cardiac phagocytes and also improved the resolution of cardiac inflammation, reduced infarct size, and preserved cardiac contractile function. Early targeting of CD47 in the myocardium after reperfusion may be a new strategy to enhance wound repair in the ischemic heart.