Abstract 16959: A Youthful Cardiomyocyte Phenotype Drives Enhanced Cardiac Recovery in Adult Spiny Mice

Abstract

Introduction: Adult mammals, including humans, experience limited recovery following myocardial infarction (MI). Recently, our group has uncovered a unique ability for enhanced cardiac recovery in adult spiny mice ( Acomys ). Methods and Results: Our preliminary studies have established appropriate similarities in heart structure and coronary anatomy between Acomys and Mus . Following the same permanent left artery descending (LAD) ligation surgery, Acomys and Mus showed a similar degree of early cardiac injury. Echocardiography and histological analyses showed more robust cardiac recovery and smaller scar area in Acomys . Moreover, Acomys exhibited a higher survival rate compared to Mus with no evidence of cardiac rupture or hypertrophy (measured by increasing heart/body weight) after MI. To investigate the mechanisms underlying this phenomenon, we isolated and quantified the size, nuclei number, and ploidy of adult cardiomyocytes (CMs) in both species (n=5 animals/group) using the Langendorff perfusion technique. Acomys CMs are significantly smaller in size compared to Mus and Acomys hearts have higher percentage of mononucleated cardiomyocytes. Using flow cytometry, we found that Acomys possess a higher percentage of diploid CMs compared to Mus . A closer examination of cardiomyocytes using electrophysiology revealed the presence of a T-type calcium current in adult Acomys CMs; a characteristic which is usually found in highly proliferative embryonic ventricular cardiomyocytes. Lastly, Acomys CMs demonstrated higher proliferative rates after injury compared to Mus . Conclusion: Taken together, our data provide strong evidence for enhanced cardiac repair in an adult mammalian model. Our results strongly suggest that Acomys maintain proliferative adult cardiomyocytes as adults and thus provide a cellular mechanism for their enhanced cardiac recovery after AMI.