| First Author | Aurora AB | Year | 2012 |
| Journal | J Clin Invest | Volume | 122 |
| Issue | 4 | Pages | 1222-32 |
| PubMed ID | 22426211 | Mgi Jnum | J:184550 |
| Mgi Id | MGI:5424306 | Doi | 10.1172/JCI59327 |
| Citation | Aurora AB, et al. (2012) MicroRNA-214 protects the mouse heart from ischemic injury by controlling Ca(2)(+) overload and cell death. J Clin Invest 122(4):1222-32 |
| abstractText | 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. |
