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      Heart Failure: Advanced Development in Genetics and Epigenetics

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      BioMed Research International
      Hindawi Publishing Corporation

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          Abstract

          Heart failure (HF) is a complex pathophysiological syndrome that arises from a primary defect in the ability of the heart to take in and/or eject sufficient blood. Genetic mutations associated with familial dilated cardiomyopathy, hypertrophic cardiomyopathy, and arrhythmogenic right ventricular cardiomyopathy can contribute to the various pathologies of HF. Therefore, genetic screening could be an approach for guiding individualized therapies and surveillance. In addition, epigenetic regulation occurs via key mechanisms, including ATP-dependent chromatin remodeling, DNA methylation, histone modification, and RNA-based mechanisms. MicroRNA is also a hot spot in HF research. This review gives an overview of genetic mutations associated with cardiomyopathy and the roles of some epigenetic mechanisms in HF.

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          Most cited references79

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          Chromatin remodelling during development.

          New methods for the genome-wide analysis of chromatin are providing insight into its roles in development and their underlying mechanisms. Current studies indicate that chromatin is dynamic, with its structure and its histone modifications undergoing global changes during transitions in development and in response to extracellular cues. In addition to DNA methylation and histone modification, ATP-dependent enzymes that remodel chromatin are important controllers of chromatin structure and assembly, and are major contributors to the dynamic nature of chromatin. Evidence is emerging that these chromatin-remodelling enzymes have instructive and programmatic roles during development. Particularly intriguing are the findings that specialized assemblies of ATP-dependent remodellers are essential for establishing and maintaining pluripotent and multipotent states in cells.
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            The long noncoding RNA CHRF regulates cardiac hypertrophy by targeting miR-489.

            Sustained cardiac hypertrophy is often accompanied by maladaptive cardiac remodeling leading to decreased compliance and increased risk for heart failure. Maladaptive hypertrophy is considered to be a therapeutic target for heart failure. MicroRNAs (miRNAs) and long noncoding RNAs (lncRNAs) have various biological functions and have been extensively investigated in past years.
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              CARL lncRNA inhibits anoxia-induced mitochondrial fission and apoptosis in cardiomyocytes by impairing miR-539-dependent PHB2 downregulation.

              Abnormal mitochondrial fission participates in the pathogenesis of many diseases. Long non-coding RNAs (lncRNAs) are emerging as new players in gene regulation, but how lncRNAs operate in the regulation of mitochondrial network is unclear. Here we report that a lncRNA, named cardiac apoptosis-related lncRNA (CARL), can suppress mitochondrial fission and apoptosis by targeting miR-539 and PHB2. The results show that PHB2 is able to inhibit mitochondrial fission and apoptosis. miR-539 is responsible for the dysfunction of PHB2 and regulates mitochondrial fission and apoptosis by targeting PHB2. Further, we show that CARL can act as an endogenous miR-539 sponge that regulates PHB2 expression, mitochondrial fission and apoptosis. Our present study reveals a model of mitochondrial fission regulation that is composed of CARL, miR-539 and PHB2. Modulation of their levels may provide a new approach for tackling apoptosis and myocardial infarction.
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                Author and article information

                Journal
                Biomed Res Int
                Biomed Res Int
                BMRI
                BioMed Research International
                Hindawi Publishing Corporation
                2314-6133
                2314-6141
                2015
                9 April 2015
                : 2015
                : 352734
                Affiliations
                Department of Cardiology, The First Affiliated Hospital, College of Medicine, Zhejiang University, No. 79, Qing-Chun Road, Hangzhou 310003, China
                Author notes

                Academic Editor: Daniele Catalucci

                Article
                10.1155/2015/352734
                4407520
                25949994
                470cb1ad-aad0-4343-81ec-d653b15d5d94
                Copyright © 2015 Jian Yang et al.

                This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

                History
                : 27 November 2014
                : 25 February 2015
                : 19 March 2015
                Categories
                Review Article

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