Gene Therapy: Targeting Cardiomyocyte Proliferation to Repopulate the Ischemic Heart

J Cardiovasc Pharmacol. 2021 Sep 1;78(3):346-360. doi: 10.1097/FJC.0000000000001072.

Abstract

Adult mammalian cardiomyocytes show scarce division ability, which makes the heart ineffective in replacing lost contractile cells after ischemic cardiomyopathy. In the past decades, there have been increasing efforts in the search for novel strategies to regenerate the injured myocardium. Among them, gene therapy is one of the most promising ones, based on recent and emerging studies that support the fact that functional cardiomyocyte regeneration can be accomplished by the stimulation and enhancement of the endogenous ability of these cells to achieve cell division. This capacity can be targeted by stimulating several molecules, such as cell cycle regulators, noncoding RNAs, transcription, and metabolic factors. Therefore, the proposed target, together with the selection of the vector used, administration route, and the experimental animal model used in the development of the therapy would determine the success in the clinical field.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Cell Cycle Proteins / genetics
  • Cell Cycle Proteins / metabolism
  • Cell Proliferation*
  • Gene Expression Regulation
  • Genetic Therapy*
  • Humans
  • Myocardial Ischemia / genetics
  • Myocardial Ischemia / pathology
  • Myocardial Ischemia / physiopathology
  • Myocardial Ischemia / therapy*
  • Myocytes, Cardiac / metabolism
  • Myocytes, Cardiac / pathology*
  • RNA, Untranslated / genetics
  • RNA, Untranslated / metabolism
  • Recovery of Function
  • Regeneration
  • Transcription Factors / genetics
  • Transcription Factors / metabolism

Substances

  • Cell Cycle Proteins
  • RNA, Untranslated
  • Transcription Factors