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Epigenetic mechanisms underlying cardiac degeneration and regeneration

  • Pankaj Chaturvedi
    Affiliations
    Department of Physiology and Biophysics, School of Medicine, University of Louisville, KY, USA
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  • Suresh C. Tyagi
    Correspondence
    Corresponding author at: Health Sciences Centre, A-1215, Department of Physiology and Biophysics, University of Louisville, School of Medicine, 500, South Preston Street, Louisville, KY 40202, USA. Tel.: +1 502 852 3381; fax: +1 502 852 6239.
    Affiliations
    Department of Physiology and Biophysics, School of Medicine, University of Louisville, KY, USA
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      Abstract

      Epigenetic modifications which are defined by DNA methylation, histone modifications and microRNA mediated gene regulation, have been found to be associated with cardiac dysfunction and cardiac regeneration but the mechanisms are unclear. MicroRNA therapies have been proposed for cardiac regeneration and proliferation of stem cells into cardiomyocytes. Cardiovascular disorders are represented by abnormal methylation of CpG islands and drugs that inhibit DNA methyltransferases such as 5-methyl Aza cytidine are under trials. Histone modifications which include acetylation, methylation, phosphorylation, ADP ribosylation, sumoylation and biotinylation are represented within abnormal phenotypes of cardiac hypertrophy, cardiac development and contractility. MicroRNAs have been used efficiently to epigenetically reprogram fibroblasts into cardiomyocytes. MicroRNAs represent themselves as potential biomarkers for early detection of cardiac disorders which are difficult to diagnose and are captured at later stages. Because microRNAs regulate circadian genes, for example a nocturnin gene of circadian clockwork is regulated by miR122, they have a profound role in regulating biological clock and this may explain the high cardiovascular risk during the morning time. This review highlights the role of epigenetics which can be helpful in disease management strategies.

      Abbreviations:

      ABCA1 (ATP binding cassette transporter A1), CAD (coronary artery disease), CREBP (cAMP (adenosine 3′5′ cyclic monophosphate) response element-binding protein), CVD (cardiovascular disease), DNMT (DNA methyltransferase), DOTIL (disruption of telomeric silencing protein), FHL1 (four and a half LIM domains 1), GNASAS (guanine nucleotide binding protein (G protein), alpha stimulating activity polypeptide), HAT (histone acetyl transferase), HDAC (histone deacetylase), HF (heart failure), HSD11B2 (hydroxysteroid (11-beta) dehydrogenase 2), IL-10 (interleukin 10), INSIGF (insulin induced gene), JMJD (Jumonji domain), LIM1 (Lin11/Isl1/Mec3 transcription factors), LINE-1 (long interspersed nucleotide elements), MEG3 (maternally expressed gene 3), MI (myocardial infarction), MTHFR (methylenetetrahydrofolate reductase), SRF (serum response factor), TBX5 (T box 5), UTX (ubiquitously transcribed tetratricopeptide repeat, X chromosome), VCAM-1 (vascular cell adhesion molecule 1)

      Keywords

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