MicroRNA-214 protects the mouse heart from ischemic injury by controlling Ca 2+ overload and cell death

Arin B Aurora, Ahmed I. Mahmoud, Xiang Luo, Brett A. Johnson, Eva Van Rooij, Satoshi Matsuzaki, Kenneth M. Humphries, Joseph A Hill, Rhonda S Bassel-Duby, Hesham A Sadek, Eric N Olson

Research output: Contribution to journalArticle

242 Citations (Scopus)

Abstract

Early reperfusion of ischemic cardiac tissue remains the most effective intervention for improving clinical outcome following myocardial infarction. However, abnormal increases in intracellular Ca 2+ during myocardial reperfusion can cause cardiomyocyte death and consequent loss of cardiac function, referred to as ischemia/ reperfusion (IR) injury. Therapeutic modulation of Ca 2+ handling provides some cardioprotection against the paradoxical effects of restoring blood flow to the heart, highlighting the significance of Ca 2+ overload to IR injury. Cardiac IR is also accompanied by dynamic changes in the expression of microRNAs (miRNAs); for example, miR-214 is upregulated during ischemic injury and heart failure, but its potential role in these processes is unknown. Here, we show that genetic deletion of miR-214 in mice causes loss of cardiac contractility, increased apoptosis, and excessive fibrosis in response to IR injury. The cardioprotective roles of miR-214 during IR injury were attributed to repression of the mRNA encoding sodium/calcium exchanger 1 (Ncx1), a key regulator of Ca 2+ influx; and to repression of several downstream effectors of Ca 2+ signaling that mediate cell death. These findings reveal a pivotal role for miR-214 as a regulator of cardiomyocyte Ca 2+ homeostasis and survival during cardiac injury.

Original languageEnglish (US)
Pages (from-to)1222-1232
Number of pages11
JournalJournal of Clinical Investigation
Volume122
Issue number4
DOIs
StatePublished - Apr 2 2012

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Heart Injuries
Reperfusion Injury
Cell Death
Cardiac Myocytes
Reperfusion
Myocardial Reperfusion
Wounds and Injuries
MicroRNAs
Cause of Death
Homeostasis
Fibrosis
Ischemia
Heart Failure
Myocardial Infarction
Apoptosis
Messenger RNA
Mouse Mirn214 microRNA

ASJC Scopus subject areas

  • Medicine(all)

Cite this

MicroRNA-214 protects the mouse heart from ischemic injury by controlling Ca 2+ overload and cell death. / Aurora, Arin B; Mahmoud, Ahmed I.; Luo, Xiang; Johnson, Brett A.; Van Rooij, Eva; Matsuzaki, Satoshi; Humphries, Kenneth M.; Hill, Joseph A; Bassel-Duby, Rhonda S; Sadek, Hesham A; Olson, Eric N.

In: Journal of Clinical Investigation, Vol. 122, No. 4, 02.04.2012, p. 1222-1232.

Research output: Contribution to journalArticle

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