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  • Cardiac Regeneration Occurs...
    Jacyniak, Kathy; Vickaryous, Matthew Kenneth

    The FASEB journal, 04/2020, Letnik: 34, Številka: S1
    Journal Article

    Abstract only Survivable injuries to the heart resolve via one of two outcomes: scar formation or tissue regeneration. Among mammals, injury to the heart typically results in the loss of contractile muscle cells (cardiomyocytes) and the formation of a non‐contractile fibrous scar. In contrast, some teleost fish and salamanders are capable of tissue‐specific regeneration, thus replacing lost or damaged cardiomyocytes. Here, we investigate the regenerative capacity of the reptilian heart, focusing on the lizard Eublepharis macularius , the leopard gecko. Unlike mammals, but similar to teleost fish, the gecko heart has a single ventricle. To determine if the ventricle was capable of regeneration, we performed a cardiac puncture (cardiocentesis) – a penetrating wound that passes through the thoracic cavity and into the heart. Cardiac punctures are readily tolerated by geckos, and normal (pre‐injury) behaviours are observed within hours of the procedure. To characterize the reparative events, we used serial histology and immunostaining for markers of cell proliferation (proliferating cell nuclear antigen, PCNA) or cell death (Terminal deoxynucleotidyl transferase dUTP nick end labeling TUNEL), each with markers for cardiomyocytes (myosin heavy chain MHC, alpha‐smooth muscle actin α‐SMA), and fibroblasts/endocardial cells (Vimentin). Prior to injury, we observed proliferating populations of both cardiomyocytes and non‐cardiomyocytes. One day post‐cardiac puncture (dpc), the wound site is characterized by cell death, a localized loss of cardiomyocytes, and the formation of a blood clot capping the puncture. Between 5 and 10 dpc, there is an increase in the number of proliferating cardiomyocytes bordering the lesion, simultaneous with an increase in proliferating non‐cardiomyocytes (cardiac fibroblasts and endothelial cells) within the wound bed itself. By 14dpc, mature cardiomyocytes have repopulated the wound site, restoring the original architecture of the myocardium. Overall, our findings reveal that regeneration of the gecko heart closely resembles that of zebrafish, and is distinct from the scar‐forming response of mammals. Support or Funding Information Natural Sciences and Engineering Research Council of Canada (NSERC) Discovery Grants 400358