Abstract
Cardiac diseases are the predominant cause of human mortality in the United States and around the world. MicroRNAs (miRNAs) are small non-coding RNAs that have been shown to modulate a wide range of biological functions under various pathophysiological conditions. miRNAs alter target expression by post-transcriptional regulation of gene expression. Numerous studies have implicated specific miRNAs in cardiovascular development, pathology, regeneration and repair. These observations suggest that miRNAs are potential therapeutic targets to prevent or treat cardiovascular diseases. This review focuses on the emerging role of miRNAs in cardiac development, pathogenesis of cardiovascular diseases, cardiac regeneration and stem cell-mediated cardiac repair. We also discuss the novel diagnostic and therapeutic potential of these miRNAs and their targets in patients with cardiac diseases.
Highlights
Heart disease is the number one cause of death for both men and women in the United States [1].By 2030, heart disease will be the leading cause of death throughout the world [2,3]
Numerous studies have shown that cardiac and circulating miRNAs are markedly altered in patients with heart failure [115,116,117]. miRNAs have emerged as a novel class of key regulators in various biological processes involved in cardiovascular diseases like fibrosis, hypertrophy, endothelial homeostasis, arrhythmias, stem cell-mediated repair and cardiac regeneration
As a result of tissue hypoxia, several key processes, such as inflammation; angiogenesis; cell death by apoptosis, autophagy and necrosis; fibrosis and hypertrophy are activated. miRNAs have been implicated in all of the above processes and might be released into the circulation, and serve as novel and sensitive biomarkers of cardiac damage [118]. These miRNAs might be packaged within exosomes and microvesicles and circulate in a stable form in many body fluids, including blood, suggesting that they might possibly act as key molecules in cell-to-cell communications and signaling [28]
Summary
Heart disease is the number one cause of death for both men and women in the United States [1]. Ischemic injury due to coronary artery disease results in permanent loss of cardiac tissue leading to adverse cardiac remodeling process and diminished contractility contributing to heart failure. Heart development and diseases are controlled by various gene regulatory networks including transcription factors, co-activators and repressors, their corresponding enhancer and promoter elements and chromatin-modifying enzymes. MicroRNAs (miRNAs) constitute a growing class of non-coding small RNAs, 20–25 nucleotides in length that act as molecular switches of gene expression and are thought to regulate complex cardiac signaling and transcriptional circuits during cardiac development and disease [4,5,6]. MiRNAs regulate gene expression on the post-transcriptional level by inhibiting the translation of protein from mRNA or by promoting the degradation of mRNA. We provide an overview of recent studies highlighting the important role of miRNAs in cardiovascular development and diseases, as well as their potential use for diagnosis, prevention, and treatment of cardiovascular diseases
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