Abstract P109: Spiny Mice Are Protected From Myocardial Infarction Induced Cardiac Pathophysiology

Abstract

Background: Despite the advancement in drug and surgical interventions, myocardial damage and associated cardiac dysfunction lead to heart failure that remains common cause of death following myocardial infarction (MI). Spiny mice (Acomys cahirinus, SM) have been shown to possess regenerating capacity following deep tissue injury without scarring ( Nature 2013 ). This led us to investigate if this regenerative property would also be preserved in the heart. Methods and Results: Adult CD1 and SM were subject to left anterior descending coronary artery ligation or sham surgeries. Proliferative cells were identified by nuclear incorporation of 5-bromodeoxyuridine (BrdU, daily, i.p.) and injection was started from 3d post MI continued to 2wks post MI. Cardiac function was assessed using echocardiography and MRI. SM exhibited 3-fold smaller infarct size (SM-MI 18.6±3.4% vs CD1-MI 76.2±3.4%, p<0.05) and better contractility measured by ejection fraction (SM-MI 77.1±6.5 vs CD1-MI 24.6±4.6, %, p<0.05) than CD1 mice. SM showed 6-fold increase in BrdU + cells in left ventricle after MI while CD1 mice had 4-fold increase (CD1-sham 11±3.5 vs CD1-MI 44±9.1 and SM-sham 16±9.8 vs SM-MI 101.1±30.9, p<0.05). Though basal cardiac ACE2 activity was not different between CD1 and SM, MI resulted in a 16% decrease in cardiac ACE2 activity in CD1-MI mice but 20% elevation of cardiac ACE2 activity in myocardial tissue in SM-MI. Conclusions: SM are protected from ischemia induced cardiac damage and dysfunction. This involves increased proliferating cardiac cells and reduction in infarct size. Thus SM could be an ideal animal model for identification of molecular and genetic circuits involved in preservation/regeneration of cardiac function with translational implication to human MI.