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World J Cardiol. Feb 26, 2016; 8(2): 211-219
Published online Feb 26, 2016. doi: 10.4330/wjc.v8.i2.211
Novel epigenetic-based therapies useful in cardiovascular medicine
Claudio Napoli, Vincenzo Grimaldi, Maria Rosaria De Pascale, Linda Sommese, Teresa Infante, Andrea Soricelli
Claudio Napoli, Vincenzo Grimaldi, Maria Rosaria De Pascale, Linda Sommese, Division of Immunohematology, Transfusion Medicine and Transplant Immunology, Department of Internal Medicine and Specialistic Unit, Azienda Ospedaliera Universitaria (AOU), Second University of Naples, 80138 Naples, Italy
Claudio Napoli, Teresa Infante, Andrea Soricelli, Institute of Diagnostic and Nuclear Development (SDN), IRCCS, 80143 Naples, Italy
Author contributions: Napoli C, Grimaldi V, De Pascale MR, Infante T, Soricelli A and Sommese L scrutinized the scientific literature; Napoli C, Grimaldi V, De Pascale MR, Soricelli A and Sommese L wrote the paper.
Conflict-of-interest statement: No potential conflicts of interest. No financial support.
Open-Access: This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
Correspondence to: Vincenzo Grimaldi, MB, BiolD, Division of Immunohematology, Transfusion Medicine and Transplant Immunology, Department of Internal Medicine and Specialistic Unit, Azienda Ospedaliera Universitaria (AOU), Second University of Naples, Piazza L. Miraglia 2, 80138 Naples, Italy. vincenzo.grimaldi@policliniconapoli.it
Telephone: +39-081-5665067 Fax: +39-081-5665092
Received: July 30, 2015
Peer-review started: July 31, 2015
First decision: September 16, 2015
Revised: December 11, 2015
Accepted: December 16, 2015
Article in press: December 18, 2015
Published online: February 26, 2016
Processing time: 206 Days and 15.9 Hours
Abstract

Epigenetic modifications include DNA methylation, histone modifications, and microRNA. Gene alterations have been found to be associated with cardiovascular diseases, and epigenetic mechanisms are continuously being studied to find new useful strategies for the clinical management of afflicted patients. Numerous cardiovascular disorders are characterized by the abnormal methylation of CpG islands and so specific drugs that could inhibit DNA methyltransferase directly or by reducing its gene expression (e.g., hydralazine and procainamide) are currently under investigation. The anti-proliferative and anti-inflammatory properties of histone deacetylase inhibitors and their cardio-protective effects have been confirmed in preclinical studies. Furthermore, the regulation of the expression of microRNA targets through pharmacological tools is still under development. Indeed, large controlled trials are required to establish whether current possible candidate antisense microRNAs could offer better therapeutic benefits in clinical practice. Here, we updated therapeutic properties, side effects, and feasibility of emerging epigenetic-based strategies in cardiovascular diseases by highlighting specific problematic issues that still affect the development of large scale novel therapeutic protocols.

Keywords: Epigenetics, Cardiovascular diseases, Heart failure, Inhibitors of histone deacetylases, Antisense microRNAs

Core tip: Recent evidence suggests that specific epigenetic regulatory mechanisms play key roles in cardiac differentiation, homeostasis, injury response, and disease development. Drug therapies that work via epigenetic mechanisms are currently limited to antineoplastic agents; large controlled trials are required to establish whether current possible candidate antisense microRNAs or histone deacetylase inhibitors could offer better therapeutic benefits in cardiovascular disease. We review recent findings on the epigenetic control of several cardiovascular diseases and the new challenges for therapeutic strategies in cardiovascular diseases.