Abstract
The injury of cardiomyocytes after ischemia-reperfusion is the main reason of cardiac dysfunction. Necrosis is one of the methods of programmed cell death and cardiomyocyte necrosis occurs in the process of reperfusion. The activation of CD137 signal is involved in various diseases. In vivo experiments proved that CD137-/- mice have less heart damage than wild-type mice after ischemia-reperfusion. In vitro experiments, we found that after inhibiting the CD137 signal, the degree of necrosis of HL-1 cells was reduced and it was caused by reducing the Ca2 + overload in the mitochondria, which caused the reduction of mPTP opening. Ca2 + overload in mitochondria induced by activation of CD137 signal was caused by increased Ca2 + released into mitochondria by activation of IP3R and increased MCU level. These results indicate that CD137 signaling aggravates cardiac ischemia-reperfusion injury by inducing myocardial cell necrosis.