29 - Structural and Functional Regeneration of the Heart Following Cryoinjury in the Lizard Eublepharis Macularius, the Leopard Gecko

Poster Board Number: 29
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Co-authors:

Catherine Williams, BSc, MSc, DVM, PhD - Assistant Professor, Animal and Veterinary Sciences, Aarhus University; Matthew Vickaryous, BSc, MSc, PhD - Professor, Biomedical Sciences, University of Guelph

Abstract Body : Injury to the adult mammalian heart results in scar formation and an irreversible decline in overall function. In contrast, some teleost fish and amphibians are capable of spontaneously regenerating lost or damaged heart tissue, thus restoring both structure and function. These investigations have revealed a crucial role for resident populations of cardiac muscle cells (cardiomyocytes) during tissue-specific repair of the ventricle. Here, we demonstrate that the lizard Eublepharis macularius (the leopard gecko) is also capable of cardiomyocyte-mediated heart regeneration. To create a necrotic lesion, we placed a pre-cooled metal probe directly on the ventricle, damaging ~20% of the myocardium. Next, we used serial histology and immunostaining to document the reparative response at multiple timepoints post-injury. Within 3 days post-cryoinjury (dpci), the lesion is characterized by cardiomyocyte loss and cell death, as well as the deposition of fibrous tissue. However, adjacent to the lesion there is a significant increase in cardiomyocyte proliferation compared to regions distantly located (p< 0.0001). Elevated rates of cardiomyocyte proliferation continue throughout the regenerative process. By 100 dpci, the site of cryoinjury is near-perfectly replaced by cardiomyocytes and rates of proliferation have returned to baseline (p= 0.8119). To document cardiac function, we used 2D echocardiography. We found that cardiac function significantly declines by 3dpci, and is most impaired by 7dpci compared to sham-operated controls (p< 0.0001). Remarkably by 60 dpci, cardiac function significantly improved (p=0.0516), and was comparable to baseline by 100 dpci (p=0.8858). Overall, we demonstrate that leopard geckos are capable of spontaneously replacing cardiomyocytes and restoring cardiac function. Our findings expand the comparative framework of heart regeneration into lizards, and provide important evidence that scar-free cardiac self-repair is more taxonomically widespread than previously understood.