Involvement of MicroRNAs in hydrogen peroxide-mediated gene regulation and cellular injury response in vascular smooth muscle cells.
ABSTRACT MicroRNAs (miRNAs) comprise a novel class of endogenous, small, noncoding RNAs that negatively regulate approximately 30% of genes in a cell via degradation or translational inhibition of their target mRNAs. However, the effects of reactive oxygen species (ROS) on miRNA expression and the roles of miRNAs in ROS-mediated gene regulation and biological functions of vascular cells are unclear. Using microarray analysis, we demonstrated that miRNAs are aberrantly expressed in vascular smooth muscle cells (VSMCs) after treatment with hydrogen peroxide (H(2)O(2)). H(2)O(2)-mediated up-regulation of microRNA-21 (miR-21) was further confirmed by quantitative real-time PCR. To determine the potential roles of miRNAs in H(2)O(2)-mediated gene regulation and cellular effects, miR-21 expression was down-regulated by miR-21 inhibitor and up-regulated by pre-miR-21. H(2)O(2)-induced VSMC apoptosis and death were increased by miR-21 inhibitor and decreased by pre-miR-21. Programmed cell death 4(PDCD4) was a direct target of miR-21 that was involved in miR-21-mediated effects on VSMCs. Pre-miR-21-mediated protective effect on VSMC apoptosis and death was blocked via adenovirus-mediated overexpression of PDCD4 without the miR-21 binding site. Moreover, activator protein 1 was a downstream signaling molecule of PDCD4 in miR-21-modulated VSMCs. The results suggest that miRNAs in VSMCs are sensitive to H(2)O(2) stimulation. miRN-21 participates in H(2)O(2)-mediated gene regulation and cellular injury response through PDCD4 and the activator protein 1 pathway. miRNAs might play a role in vascular diseases related to ROS.
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ABSTRACT: Cardiovascular diseases are currently the main cause of morbidity and mortality worldwide. Ischemic heart disease, in particular, is responsible for the majority of cardiac-related deaths. Given the negligible regenerative potential of the human myocardium, there is a strong need for therapeutic strategies aiming at enhancing cardiomyocyte survival and proliferation following injury or at inhibiting their death. MicroRNAs (miRNAs) are small non-coding RNA molecules regulating gene expression at a post-transcriptional level with important functions in cardiovascular physiology and disease. It has been demonstrated that miRNAs can influence the ability of cardiomyocytes to enter the cell cycle and/or escape from death pathways. Additionally, long non coding-RNAs could be involved in such pathways. This review summarizes recent evidences on noncoding RNAs regulating proliferation and death of cardiomyocytes representing a future therapeutic for the treatment of heart diseases. This article is part of a Special Issue entitled SI: Non-coding RNAs.Journal of Molecular and Cellular Cardiology 02/2015; DOI:10.1016/j.yjmcc.2015.02.002 · 5.22 Impact Factor
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ABSTRACT: Eukaryotic gene expression is tightly regulated transcriptionally and post-transcriptionally by a host of noncoding (nc)RNAs. The best-studied class of short ncRNAs, microRNAs, mainly repress gene expression post-transcriptionally. Long noncoding (lnc)RNAs, which comprise RNAs differing widely in length and function, can regulate gene transcription as well as post-transcriptional mRNA fate. Collectively, ncRNAs affect a broad range of age-related physiologic deteriorations and pathologies, including reduced cardiovascular vigor and age-associated cardiovascular disease. This review presents an update of our understanding of regulatory ncRNAs contributing to cardiovascular health and disease as a function of advancing age. We will discuss (1) regulatory ncRNAs that control aging-associated cardiovascular homeostasis and disease, (2) the concepts, approaches, and methodologies needed to study regulatory RNAs in cardiovascular aging and (3) the challenges and opportunities that age-associated regulatory ncRNAs present in cardiovascular physiology and pathology. Copyright © 2015. Published by Elsevier Ltd.Journal of Molecular and Cellular Cardiology 01/2015; 157. DOI:10.1016/j.yjmcc.2015.01.011 · 5.22 Impact Factor
Medicine & Science in Sports & Exercise 01/2010; 42:20. DOI:10.1249/01.MSS.0000389522.75648.b9 · 4.46 Impact Factor