The Role of Non-coding RNAs in Ischemic Myocardial Reperfusion Injury

Vince Siebert, Joseph Allencherril, Yumei Ye, Xander H.T. Wehrens, Yochai Birnbaum

Research output: Contribution to journalArticle

4 Scopus citations

Abstract

MicroRNAs (miRNA) are non-coding RNAs that regulate gene expression in up to 90% of the human genome through interactions with messenger RNA (mRNA). The expression of miRNAs varies and changes in diseased and healthy states, including all stages of myocardial ischemia-reperfusion and subsequent ischemia-reperfusion injury (IRI). These changes in expression make miRNAs an attractive potential therapeutic target. Herein, we review the differences in miRNA expression prior to ischemia (including remote ischemic conditioning and ischemic pre-conditioning), the changes during ischemia-reperfusion, and the changes in miRNA expression after IRI, with an emphasis on inflammatory and fibrotic pathways. Additionally, we review the effects of manipulating the levels of certain miRNAs on changes in infarct size, inflammation, remodeling, angiogenesis, and cardiac function after either ischemia-reperfusion or permanent coronary ligation. Levels of target miRNA can be increased using molecular mimics (“agomirs”), or can be decreased by using “antagomirs” which are antisense molecules that act to bind and thus inactivate the target miRNA sequence. Other non-coding RNAs, including long non-coding RNAs and circular RNAs, also regulate gene expression and have a role in the regulation of IRI pathways. We review the mechanisms and downstream effects of the miRNAs that have been studied as therapy in both permanent coronary ligation and ischemia-reperfusion models.

Original languageEnglish (US)
Pages (from-to)489-498
Number of pages10
JournalCardiovascular Drugs and Therapy
Volume33
Issue number4
DOIs
StatePublished - Aug 15 2019

Keywords

  • Ischemic heart disease
  • Reperfusion injury
  • microRNA

ASJC Scopus subject areas

  • Pharmacology
  • Cardiology and Cardiovascular Medicine
  • Pharmacology (medical)

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