Identifying the key regulators that promote cell-cycle activity in the hearts of early neonatal pigs after myocardial injury

Academic Article

Abstract

  • Mammalian cardiomyocytes exit the cell cycle shortly after birth. As a result, an occurrence of coronary occlusion-induced myocardial infarction often results in heart failure, postinfarction LV dilatation, or death, and represents one of the most significant public health morbidities worldwide. Interestingly however, the hearts of neonatal pigs have been shown to regenerate following an acute myocardial infarction (MI) occuring on postnatal day 1 (P1); a recovery period which is accompanied by an increased expression of markers for cell-cycle activity, and suggests that early postnatal myocardial regeneration may be driven in part by the MI-induced proliferation of pre-existing cardiomyocytes. In this study, we identified signaling pathways known to regulate the cell cycle, and determined of these, the pathways persistently upregulated in response to MI injury. We identified five pathways (mitogen associated protein kinase [MAPK], Hippo, cyclic [cAMP], Janus kinase/signal transducers and activators of transcription [JAK-STAT], and Ras) which were comprehensively upregulated in cardiac tissues collected on day 7 (P7) and/or P28 of the P1 injury hearts. Several of the initiating master regulators (e.g., CSF1/CSF1R, TGFB, and NPPA) and terminal effector molecules (e.g., ATF4, FOS, RELA/B, ITGB2, CCND1/2/3, PIM1, RAF1, MTOR, NKF1B) in these pathways were persistently upregulated at day 7 through day 28, suggesting there exists at least some degree of regenerative activity up to 4 weeks following MI at P1. Our observations provide a list of key regulators to be examined in future studies targeting cell-cycle activity as an avenue for myocardial regeneration.
  • Authors

    Published In

  • PLoS ONE  Journal
  • Digital Object Identifier (doi)

    Author List

  • Zhang E; Nguyen T; Zhao M; Dang SDH; Chen JY; Bian W; Walcott GP
  • Volume

  • 15
  • Issue

  • 7 July