INTRINSIC INCREASED ACE2 EXPRESSION PROTECTS SPINY MOUSE ACOMYS CAHIRINUS AGAINST ISCHEMIC‐INDUCED CARDIAC DYSFUNCTION

Abstract

Angiotensin converting enzyme 2 (ACE2), a key component of the renin angiotensin system (RAS), is a potential therapeutic target for ischemic heart disease as it protects cardiovascular function. Recently, extensive evidence points to a significant role of ACE2 in regulation of hematopoiesis and vasculogenesis via correction of endothelial progenitor cell dysfunction and increases in the number of cardiac and endothelial progenitor cells after ischemic injury. Spiny mice (Acomys cahirinus, SM) possess lizard‐like abilities when a large portion of skin is “torn away” the deep tissue injury heals rapidly by regenerating complete hair follicles, dermis, epidermis, sebaceous glands, adipose tissue, microvessels, smooth muscle and skeletal muscle of the panniculus carnosus without scaring (Nature 2013). This skin auto to my provides an effective defense against predators. We tested the cardiac regenerative capacity of SM using a myocardial infarction (MI) model. Following ligation of left anterior descending coronary artery, the SM exhibited smaller infarct size (SM‐MI 20% of left ventricular free wall vs CD1‐MI 50%, p<0.05) with preserved ejection fraction vs CD1 mice (SM‐MI 62 ± 2% vs CD1‐MI 32± 7%, p<0.05). At baseline ACE2 activity in SM sham was elevated 12% in myocardial tissue and 23% in plasma vs CDl sham (both, p<0.05). MI resulted in a 37% decrease in ACE2 activity in CD1 mice (p<0.05 vs baseline and vs SM‐MI). Interestingly, SM exhibited further elevation of ACE2 activity (7%) in myocardial tissue following MI, while plasma ACE2 activity remained unchanged after MI. Collectively, our findings suggest that ACE2 is likely to be modulating, at least in part, the myocardial preservation/regeneration process in the SM.Support or Funding Information2 UM1 HL087366‐06, R01 HL056921, HL033610, and UL1 TR000064 from the National Institutes of Health