Midkine and Heart Failure

The molecular mechanisms of midkine (MK) in myocardial damage and the possibility of clinical application of MK for heart failure were assessed. In the acute phase of cardiac ischemia/reperfusion (I/R) injury of mice, MK showed an anti-apoptotic reaction for cardiomyocytes through Bcl-2 and ERK activation. In addition, the damage from pig acute I/R injury was suppressed by catheter injection of MK into the coronary artery. The pig model is the faithful one of clinical case, and thus MK has been suggested to be an important candidate material for the treatment of acute myocardial infarction. MK also prevented ventricular remodeling and improved long-term survival after myocardial infarction in mouse and rat chronic models. The mechanisms of these effects involved MK-induced angiogenesis via the PI3/Akt pathway. Moreover, MK inhibited the cardiac remodeling of non-ischemic myocardial damage induced by rapid pacing in rabbits. MK is thus a potentially important new molecular target for treatment and prevention of heart failure.