Cardiac Ctrp9 Regulates Endoplasmic Reticulum Calreticulin Retrotranslocation To Protect Against Myocardial Ischemia/Reperfusion Injury

Background: Cardiokines are a group of heart produced-secretomes that maintain cardiac function and modulate pathologic remodeling. CTRP9 is a newly identified cardiokine. However, the biological function of cardiac generated CTRP9 remains unclear. Methods and Results: Mice were subjected to myocardial ischemia/reperfusion (MI/R) and gene interfering methods were used. Compare to vehicle, inhibition of cardiac CTRP9 via intra-myocardial siRNA injection significantly reduced left ventricular ejection fraction (LVEF, 28.6%, P<0.01), augmented infarct size (P<0.05) and increased apoptosis post-MI/R (P<0.05). In contrast, overexpression of CTRP9 via lentivirus reversely improved MI/R-induced cardiac dysfunction and apoptosis (P<0.05, respectively). Notably, cardiac CTRP9 overexpression up-regulated endoplasmic reticulum (ER) protein calreticulin (CRT) expression (P<0.01). Co-IP results demonstrated that cardiac CTRP9 interacted with CRT and confocal images revealed that CTRP9 colocalized with CRT in the cytop...