Abstract Body (Do not enter title and authors here): Introduction: Heart attacks and the inability of the adult mammalian heart to regenerate after injury lead to recurrent heart attacks, heart failure, and high mortality within five years. We have recently shown that Acomys have the ability to preserve cardiac tissue in contrast to other mammals. We hypothesize that Acomys cardiac resident macrophages are cardioprotective and enhance myocardial preservation in response to injury through a pro-angiogenic response.
Methods: We depleted resident cardiac macrophages using two weekly doses of anti-CD115 antibody starting two weeks before performing myocardial infarction (MI) through permanent left anterior descending artery (LAD) ligation. Cardiac function was assessed using echocardiography. Capillary density and cardiac fibrosis were assessed using immunohistochemistry. We performed RNASeq to examine the role of resident macrophage depletion on cardiac tissue in Acomys.
Results: This preferential depletion of resident macrophages resulted in a significant reduction in angiogenesis and capillary density in the ischemic zone in resident macrophage depleted mice. RNAseq data also showed increased pro-inflammatory and pro-fibrotic gene expression and reduced pro-angiogenic gene expression with resident macrophage depletion after cardiac injury.
Conclusions: These studies highlight the critical role of resident macrophages in post-MI cardiac recovery in Acomys. Current studies in our laboratory are exploring the underlying mechanism behind the protective effects of resident cardiac macrophages in Acomys.