MicroRNA-214 protects the mouse heart from ischemic injury by controlling Ca²⁺ overload and cell death.
J Clin Invest, 2012/4;122(4):1222-32.
Aurora AB[1], Mahmoud AI, Luo X, Johnson BA, van Rooij E, Matsuzaki S, Humphries KM, Hill JA, Bassel-Duby R, Sadek HA, Olson EN
Affiliations
PMID: 22426211
Impact factor: 19.456
Abstract
Early reperfusion of ischemic cardiac tissue remains the most effective intervention for improving clinical outcome following myocardial infarction. However, abnormal increases in intracellular Ca²⁺ during myocardial reperfusion can cause cardiomyocyte death and consequent loss of cardiac function, referred to as ischemia/reperfusion (IR) injury. Therapeutic modulation of Ca²⁺ handling provides some cardioprotection against the paradoxical effects of restoring blood flow to the heart, highlighting the significance of Ca²⁺ 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 Ca²⁺ influx; and to repression of several downstream effectors of Ca²⁺ signaling that mediate cell death. These findings reveal a pivotal role for miR-214 as a regulator of cardiomyocyte Ca²⁺ homeostasis and survival during cardiac injury.
MeSH terms
Animals; Apoptosis; Calcium Signaling; Cells, Cultured; Gene Deletion; Gene Expression Regulation; Gene Knockdown Techniques; Mice; Mice, Knockout; MicroRNAs; Mitochondria; Myocardial Contraction; Myocardial Reperfusion Injury; Myocardium; Myocytes, Cardiac; RNA, Messenger; Rats; Rats, Sprague-Dawley; Sodium-Calcium Exchanger
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