Next Article in Journal
Microwave-Assisted Synthesis of Glutathione-Capped CdTe/CdSe Near-Infrared Quantum Dots for Cell Imaging
Next Article in Special Issue
Urotensin II Protects Cardiomyocytes from Apoptosis Induced by Oxidative Stress through the CSE/H2S Pathway
Previous Article in Journal
Gene Expression Signature in Endemic Osteoarthritis by Microarray Analysis
Previous Article in Special Issue
Prenatal Exposure to Lipopolysaccharide Results in Myocardial Fibrosis in Rat Offspring
Article Menu
Issue 5 (May) cover image

Export Article

Open AccessArticle
Int. J. Mol. Sci. 2015, 16(5), 11482-11499; doi:10.3390/ijms160511482

Anti-Fibrotic Effects of Class I HDAC Inhibitor, Mocetinostat Is Associated with IL-6/Stat3 Signaling in Ischemic Heart Failure

Cardiovascular Research Laboratory, Banner Sun Health Research Institute, Sun City, AZ 85351, USA
*
Author to whom correspondence should be addressed.
Academic Editor: H. W. M. Niessen
Received: 9 March 2015 / Revised: 26 April 2015 / Accepted: 5 May 2015 / Published: 19 May 2015
(This article belongs to the Special Issue Improvement of Cardiac Function in Heart Failure)
View Full-Text   |   Download PDF [1126 KB, uploaded 21 May 2015]   |  

Abstract

Background: Recent studies have linked histone deacetylases (HDAC) to remodeling of the heart and cardiac fibrosis in heart failure. However, the molecular mechanisms linking chromatin remodeling events with observed anti-fibrotic effects are unknown. Here, we investigated the molecular players involved in anti-fibrotic effects of HDAC inhibition in congestive heart failure (CHF) myocardium and cardiac fibroblasts in vivo. Methods and Results: MI was created by coronary artery occlusion. Class I HDACs were inhibited in three-week post MI rats by intraperitoneal injection of Mocetinostat (20 mg/kg/day) for duration of three weeks. Cardiac function and heart tissue were analyzed at six week post-MI. CD90+ cardiac fibroblasts were isolated from ventricles through enzymatic digestion of heart. In vivo treatment of CHF animals with Mocetinostat reduced CHF-dependent up-regulation of HDAC1 and HDAC2 in CHF myocardium, improved cardiac function and decreased scar size and total collagen amount. Moreover, expression of pro-fibrotic markers, collagen-1, fibronectin and Connective Tissue Growth Factor (CTGF) were reduced in the left ventricle (LV) of Mocetinostat-treated CHF hearts. Cardiac fibroblasts isolated from Mocetinostat-treated CHF ventricles showed a decrease in expression of collagen I and III, fibronectin and Timp1. In addition, Mocetinostat attenuated CHF-induced elevation of IL-6 levels in CHF myocardium and cardiac fibroblasts. In parallel, levels of pSTAT3 were reduced via Mocetinostat in CHF myocardium. Conclusions: Anti-fibrotic effects of Mocetinostat in CHF are associated with the IL-6/STAT3 signaling pathway. In addition, our study demonstrates in vivo regulation of cardiac fibroblasts via HDAC inhibition. View Full-Text
Keywords: congestive heart failure; myocardial infarction; Mocetinostat; cardiac fibrosis; HDAC congestive heart failure; myocardial infarction; Mocetinostat; cardiac fibrosis; HDAC
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. (CC BY 4.0).

Supplementary material

Scifeed alert for new publications

Never miss any articles matching your research from any publisher
  • Get alerts for new papers matching your research
  • Find out the new papers from selected authors
  • Updated daily for 49'000+ journals and 6000+ publishers
  • Define your Scifeed now

SciFeed Share & Cite This Article

MDPI and ACS Style

Nural-Guvener, H.; Zakharova, L.; Feehery, L.; Sljukic, S.; Gaballa, M. Anti-Fibrotic Effects of Class I HDAC Inhibitor, Mocetinostat Is Associated with IL-6/Stat3 Signaling in Ischemic Heart Failure. Int. J. Mol. Sci. 2015, 16, 11482-11499.

Show more citation formats Show less citations formats

Related Articles

Article Metrics

Article Access Statistics

1

Comments

[Return to top]
Int. J. Mol. Sci. EISSN 1422-0067 Published by MDPI AG, Basel, Switzerland RSS E-Mail Table of Contents Alert
Back to Top