Promoting cardiomyocyte proliferation for myocardial regeneration in large mammals

Thanh Nguyen, Manuel Rosa-Garrido, Hesham Sadek, Daniel J. Garry, Jianyi (Jay) Zhang

Research output: Contribution to journalReview articlepeer-review

Abstract

From molecular and cellular perspectives, heart failure is caused by the loss of cardiomyocytes—the fundamental contractile units of the heart. Because mammalian cardiomyocytes exit the cell cycle shortly after birth, the cardiomyocyte damage induced by myocardial infarction (MI) typically leads to dilatation of the left ventricle (LV) and often progresses to heart failure. However, recent findings indicate that the hearts of neonatal pigs completely regenerated the cardiomyocytes that were lost to MI when the injury occurred on postnatal day 1 (P1). This recovery was accompanied by increases in the expression of markers for cell-cycle activity in cardiomyocytes. These results suggest that the repair process was driven by cardiomyocyte proliferation. This review summarizes findings from recent studies that found evidence of cardiomyocyte proliferation in 1) the uninjured hearts of newborn pigs on P1, 2) neonatal pig hearts after myocardial injury on P1, and 3) the hearts of pigs that underwent apical resection surgery (AR) on P1 followed by MI on postnatal day 28 (P28). Analyses of cardiomyocyte single-nucleus RNA sequencing data collected from the hearts of animals in these three experimental groups, their corresponding control groups, and fetal pigs suggested that although the check-point regulators and other molecules that direct cardiomyocyte cell-cycle progression and proliferation in fetal, newborn, and postnatal pigs were identical, the mechanisms that activated cardiomyocyte proliferation in response to injury may differ from those that regulate cardiomyocyte proliferation during development.

Original languageEnglish (US)
Pages (from-to)52-60
Number of pages9
JournalJournal of Molecular and Cellular Cardiology
Volume188
DOIs
StatePublished - Mar 2024

Bibliographical note

Publisher Copyright:
© 2024 The Authors

Keywords

  • Acute myocardial infarction
  • Apical resection
  • Cardiomyocyte
  • Myocardial
  • Porcine
  • Proliferation.
  • Regeneration

PubMed: MeSH publication types

  • Journal Article
  • Review
  • Research Support, N.I.H., Extramural

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