Optimizing cardiac ischemic preconditioning and postconditioning via epitranscriptional regulation

Richa Saxena, Neal L. Weintraub, Yaoliang Tang

Research output: Contribution to journalArticle

Abstract

Ischemic cardiac preconditioning protects the heart during myocardial infarction by activating critical cardioprotective genes such as eNOS, SOD, and HO-1. Clinical trials only show marginal effects of conventional preconditioning strategies, however, in part due to transient activation of cardioprotective genes. Recent studies have shown that N6-methyladenosine (m6A) mRNA methylation is the most abundant RNA modification in eukaryotes, and governs mRNA stability and, in turn, the level of protein expression. We hypothesize that regulation of m6A mRNA methylation levels of cardioprotective mRNAs will result in stable expression of the cardioprotective proteins, rendering ischemic cardiac preconditioning more robust and reducing infarct size. To test this hypothesis, we will test the effects of introducing m6A methylases/demethylases into ischemic preconditioned/post conditioned hearts and subjecting them to myocardial infarction. We will assess the half-life of key cardioprotective mRNAs (e.g., eNOS, SOD, and HO-1) and cardiac apoptosis to determine which m6A methylases/demethylases have a synergistic effect on cardiac preconditioning.

Original languageEnglish (US)
Article number109451
JournalMedical Hypotheses
Volume135
DOIs
StatePublished - Feb 2020

Fingerprint

Ischemic Postconditioning
Ischemic Preconditioning
Messenger RNA
Methylation
Myocardial Infarction
RNA Stability
Eukaryota
Transcriptional Activation
Half-Life
Proteins
Clinical Trials
RNA
Apoptosis
Genes

Keywords

  • Cardiac postconditioning
  • Cardiac preconditioning
  • Epitranscriptome
  • m6A

ASJC Scopus subject areas

  • Medicine(all)

Cite this

Optimizing cardiac ischemic preconditioning and postconditioning via epitranscriptional regulation. / Saxena, Richa; Weintraub, Neal L.; Tang, Yaoliang.

In: Medical Hypotheses, Vol. 135, 109451, 02.2020.

Research output: Contribution to journalArticle

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