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Cardiovasc Res. 2017 Jun 1;113(7):725-736. doi: 10.1093/cvr/cvx070.

Epigenomic and transcriptomic approaches in the post-genomic era: path to novel targets for diagnosis and therapy of the ischaemic heart? Position Paper of the European Society of Cardiology Working Group on Cellular Biology of the Heart.

Author information

1
Department of Advanced Biomedical Sciences, Federico II University, Via Pansini 5, 80131 Naples, Italy.
2
Center for Complex Networks Research and Department of Physics, Northeastern University, Boston, MA, USA.
3
Center for Cancer Systems Biology (CCSB) and Department of Cancer Biology, Dana-Farber Cancer Institute, Boston, MA, USA.
4
Center for Network Science, Central European University, Budapest, Hungary.
5
Department of Medicine, and Division of Network Medicine, Brigham and Womens Hospital, Harvard Medical School, 75 Francis Street, Boston, MA 02115, USA.
6
Department of Cardiovascular Medicine, Humanitas Research Hospital and Humanitas University, Rozzano, Italy.
7
Institute of Genetic and Biomedical Research, National Research Council of Italy, Rozzano, Milan, Italy.
8
The Hatter Cardiovascular Institute, Institute of Cardiovascular Science, University College London, London, UK.
9
Department of Cardiology, CARIM School for Cardiovascular Diseases, Maastricht University, 6229 ER Maastricht, The Netherlands.
10
Institute for Cardiovascular Regeneration, University Frankfurt, Frankfurt, Germany.
11
German Center for Cardiovascular Research (DZHK), RheinMain, Germany.
12
Experimental Renal and Cardiovascular Research, Department of Nephropathology, Institute of Pathology, Friedrich-Alexander-Universität Erlangen-Nürnberg (FAU), Erlangen, Germany.
13
The Hatter Cardiovascular Institute, University College London, London, UK.
14
The National Institute of Health Research University College London Hospitals Biomedical Research Centre, London, UK.
15
Cardiovascular and Metabolic Disorders Program, Duke-National University of Singapore, Singapore.
16
National Heart Research Institute Singapore, National Heart Centre Singapore, Singapore.
17
Yong Loo Lin School of Medicine, National University Singapore, Singapore.
18
Barts Heart Centre, St Bartholomew's Hospital, London, UK.
19
Departments of Medicine (Cardiology) and Molecular Biology, UT Southwestern Medical Center, Dallas, TX, USA.
20
Division of Heart and Lungs, Hubrecht Institute, University Medical Center Utrecht, Utrecht, The Netherlands.
21
UMC Utrecht Regenerative Medicine Center and Hubrecht Institute, Utrecht, The Netherlands.
22
Hatter Cardiovascular Research Institute, University of Cape Town, Cape Town, South Africa.
23
Neufeld Cardiac Research Institute, Tel-Aviv University, Tel-Aviv, Israel.
24
Tamman Cardiovascular Research Institute, Sheba Medical Center; Sheba Center for Regenerative Medicine, Stem Cell, and Tissue Engineering, Tel Hashomer, Israel.
25
Center of Aging Sciences and Translational Medicine - CESI-MeT, "G. d'Annunzio" University, Chieti, Italy; Institute of Cardiology, Department of Neurosciences, Imaging, and Clinical Sciences, "G. d'Annunzio" University, Chieti, Italy.
26
The Texas Heart Institute and Center for Cardiovascular Biology and Atherosclerosis Research, Department of Internal Medicine, The University of Texas Health Science Center at Houston, Houston, TX, USA.
27
King's British Heart Foundation Centre, King's College London, London, UK.
28
Department of Cardiology, Institut MITOVASC, University of Angers, University Hospital of Angers, Angers, France.
29
Cardiology and UMC Utrecht Regenerative Medicine Center, University Medical Center Utrecht, Utrecht, The Netherlands.
30
Institute of Physiology, Justus Liebig University Giessen, Giessen, Germany.
31
Institute of Molecular and Translational Therapeutic Strategies, Hannover Medical School, Hannover, Germany.
32
Department of Medical Biology, Faculty of Health Sciences, UiT The Arctic University of Norway, Tromsø, Norway.
33
Department of Pharmacology and Pharmacotherapy, Semmelweis University, Budapest, Hungary.
34
Cardiovascular Research Group, Department of Biochemistry, University of Szeged, Szeged, Hungary.
35
Pharmahungary Group, Szeged, Hungary.

Abstract

Despite advances in myocardial reperfusion therapies, acute myocardial ischaemia/reperfusion injury and consequent ischaemic heart failure represent the number one cause of morbidity and mortality in industrialized societies. Although different therapeutic interventions have been shown beneficial in preclinical settings, an effective cardioprotective or regenerative therapy has yet to be successfully introduced in the clinical arena. Given the complex pathophysiology of the ischaemic heart, large scale, unbiased, global approaches capable of identifying multiple branches of the signalling networks activated in the ischaemic/reperfused heart might be more successful in the search for novel diagnostic or therapeutic targets. High-throughput techniques allow high-resolution, genome-wide investigation of genetic variants, epigenetic modifications, and associated gene expression profiles. Platforms such as proteomics and metabolomics (not described here in detail) also offer simultaneous readouts of hundreds of proteins and metabolites. Isolated omics analyses usually provide Big Data requiring large data storage, advanced computational resources and complex bioinformatics tools. The possibility of integrating different omics approaches gives new hope to better understand the molecular circuitry activated by myocardial ischaemia, putting it in the context of the human 'diseasome'. Since modifications of cardiac gene expression have been consistently linked to pathophysiology of the ischaemic heart, the integration of epigenomic and transcriptomic data seems a promising approach to identify crucial disease networks. Thus, the scope of this Position Paper will be to highlight potentials and limitations of these approaches, and to provide recommendations to optimize the search for novel diagnostic or therapeutic targets for acute ischaemia/reperfusion injury and ischaemic heart failure in the post-genomic era.

KEYWORDS:

Big Data; Bioinformatics; Multiomics; Network analysis; Omics; Tailored medicine

PMID:
28460026
PMCID:
PMC5437366
DOI:
10.1093/cvr/cvx070
[Indexed for MEDLINE]
Free PMC Article

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