Cardiac Regeneration in Neonatal Porcine Heart
Description: In contrast to cardiomyocytes from lower vertebrates, adult mammalian cardiomyocytes possess very limited regenerative potential as a result of cell cycle exit. However, neonatal mice retain regenerative capacity, which is lost by day 7 after birth. We have recently shown that neonatal pigs can also regenerate lost myocardium shortly after birth in response to myocardial infarction. Hearts of 1-day-old pigs (P1) can regrow functionally and structurally normal myocardium following myocardial infarction. This regrowth is mediated by the proliferation of preexisting cardiomyocytes, which does not occur when cardiomyocytes permanently exit the cell cycle. Mechanisms underlying the injury-mounted regenerative response especially in large mammals have not been fully understood. Recent publications emphasized the importance of revascularization and autonomic innervation for cardiac regeneration in zebrafish and neonatal mouse hearts. Besides their function to provide nutrients, transport metabolites, and enable adaptation to stress, it is unknown whether vascular and neuronal cells also promote cardiomyocyte proliferation. In addition, these interesting studies were done in fish and rodents. Whether similar mechanisms contribute to cardiac regeneration in large mammals remain unknown. The main objectives of this application are to examine: 1) to what extent early revascularization and autonomic innervation contribute to injury-mounted cardiac regeneration in neonatal pigs; 2) mechanisms by which revascularization and autonomic innervation contribute to cardiac regeneration; 3) whether cardiomyocyte proliferation and regeneration window can be extended by manipulating revascularization and autonomic innervation. We will exploit the high regenerative capacity of neonatal pig heart model to experimentally address the role of nonmyocytes in cardiac regeneration in large mammals.
Funder: American Heart Association
Amount: $300,000
Funding type: research
Funder scheme: Transformational Project Award
Start date: 2021-01-01
End date: 2022-08-31
Investigators: Wuqiang Zhu, Wuqiang Zhu
Institution: Mayo Clinic Arizona
Funded outputs count: 9
Funder award ID: 20TPA35490001
OpenAlex ID: G5187001972