Abstract
BackgroundLong non-coding RNAs (lncRNAs) constitute a novel class of non-coding RNAs. LncRNAs regulate gene expression, thus having the possibility to modulate disease progression. In this study, we investigated the changes of lncRNAs expression in the heart after myocardial infarction (MI).ResultsAdult male C57/BL6 mice were subjected to coronary ligation or sham operation. In a derivation group of 4 MI and 4 sham-operated mice sacrificed 24 hours after surgery, microarray analysis showed that MI was associated with up-regulation of 20 lncRNAs and down-regulation of 10 lncRNAs (fold-change >2). Among these, 2 lncRNAs, called myocardial infarction-associated transcript 1 (MIRT1) and 2 (MIRT2), showed robust up-regulation in the MI group: 5-fold and 13-fold, respectively. Up-regulation of these 2 lncRNAs after MI was confirmed by quantitative PCR in an independent validation group of 8 MI and 8 sham-operated mice (9-fold and 16-fold for MIRT1 and MIRT2, P < 0.001). In a time-course analysis involving 21 additional MI mice, the expression of both lncRNAs peaked 24 hours after MI and returned to baseline after 2 days. In situ hybridization revealed an up-regulation of MIRT1 expression in the left ventricle of MI mice. Expression of MIRT1 and MIRT2 correlated with the expression of multiple genes known to be involved in left ventricular remodeling. Mice with high level of expression of MIRT1 and MIRT2 had a preserved ejection fraction.ConclusionMyocardial infarction induces important changes in the expression of lncRNAs in the heart. This study motivates further investigation of the role of lncRNAs in left ventricular remodeling.Electronic supplementary materialThe online version of this article (doi: 10.1186/1471-2164-15-460) contains supplementary material, which is available to authorized users.
Highlights
Long non-coding RNAs constitute a novel class of non-coding RNAs
Left ventricular function was assessed in all mice by FDG-PET 24 hours after surgery
Considering that infarcted areas display less than 50% FDG uptake, we calculated infarct size for each mice, which is the number of infarcted segments related to the total number of 17 segments
Summary
Long non-coding RNAs (lncRNAs) constitute a novel class of non-coding RNAs. LncRNAs regulate gene expression, having the possibility to modulate disease progression. Oxygen and nutrient deprivation to the heart induces severe damages, which can be of multiple types: necrosis or apoptosis of cardiac cells, cardiomyocyte hypertrophy, or fibrosis. Part of these damages can be induced by a de-regulation of gene expression. Since the initial sequencing of the human genome more than a decade ago [3,4], huge progress has been made in the understanding of its complexity.
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