MicroRNAs: New Players in Cardiac Injury and Protection

Abstract

MicroRNAs (miRNAs) have emerged as a novel class of endogenous, small, noncoding RNAs that negatively regulate gene expression via degradation or translational inhibition of their target mRNAs. Over 700 miRNAs have been identified and sequenced in humans, and the number of miRNA genes is estimated at more than 1000. Individual miRNA is functionally important as a transcription factor because it has the ability to regulate the expression of multiple genes through binding to its target with imperfect or perfect complement. In the heart, miRNAs have been involved in several clinical scenarios, such as ischemia/reperfusion (I/R) injury and heart failure suggesting that regulation of their function could be used as a novel cardioprotective strategy. In particular, miRNA-1, miRNA-21, miRNA-24, miRNA-29, miRNA-92a, miRNA-126, miRNA-133, miRNA-320, miRNA-199a, miRNA-208, and miRNA-195 have been shown to be regulated after I/R injury. Because tissue miRNAs can be released into circulating blood, they also offer exciting new opportunities for developing sensitive biomarkers, including miRNA-1, miRNA-126, miR-208, and miRNA-499, for acute myocardial infarction and other cardiac diseases.

Cardioprotection From Ischemia/Reperfusion Injury

“…IR stimuli alter the expression of microRNAs. 94 Recent studies revealed that microRNAs are implicated in cardiac pathology including hypertrophy and failure 95 and IR injury 96 (Table 2). Therefore, microRNAs are novel promising therapeutic targets for IHDs.…”

Myocardial connexin-43 and PKC signalling are involved in adaptation of the heart to irradiation-induced injury: Implication of miR-1 and miR-21

“…MicroRNAs fundamentally influence the pathogenesis of various events (Kukreja et al 2011), including adverse cardiac remodelling such as hypertrophy and fibrosis (van Rooij et al 2012). These myocardial alterations compromise cell-to-cell contacts and Cx43 channels mediated communication in diseased or aged heart and promote the occurrence of malignant arrhythmias (Tribulova et al 2008;Jansen et al 2012;Radosinska et al 2013).…”

A „szabad” nukleinsavak jelentősége a noninvazív diagnosztikában

“…Újabb vizsgálatok szerint legalább 20 mikro-RNS szintje mutat összefüg-gést az AMI-val és ezekből legalább 9 a troponinszintekkel [34]. A miR-1, miR-133, miR-208 és a miR499 a legjobban tanulmányozott molekulák koszorúér-betegségekben és akut myocardialis infarctusban [35]. A sérült myocardiumból kiáramló mikro-RNS-ek mellett az akut esemény után emelkedett szintet mutató miRNS-ek részben extracardialis eredetűek, mint például a miR30c, miR-145, amelyek ugyanakkor összefüggést mutattak az infarktus méretével.…”