Novel Histone Deacetylase Inhibitor Modulates Cardiac Peroxisome Proliferator-Activated Receptors and Inflammatory Cytokines in Heart Failure

Baigalmaa Lkhagva, Yung Kuo Lin, Yu Hsun Kao, Tze Fan Chazo, Cheng Chih Chung, Shih Ann Chen, Yi Jen Chen

Research output: Contribution to journalArticlepeer-review

16 Citations (Scopus)

Abstract

Background: Heart failure (HF) affects cardiac metabolism and inflammation. Histone deacetylases (HDACs) play a critical role in cardiac pathophysiology. This study investigated whether HDAC inhibition can regulate HF by modifying cardiac inflammation and peroxisome proliferator-activated receptor (PPAR) isoforms. Methods: Echocardiography, electrocardiography, ELISA and Western blot were performed in rats with isoproterenol-induced HF, with and without orally administered MPT0E014 (a novel HDAC inhibitor, 50 mg/kg for 7 consecutive days). Results: The left ventricles (LVs) of HF rats expressed significantly higher levels of HDAC1, HDAC2, HDAC3, HDAC4 and HDAC6 than the healthy LVs did. HF rats treated with MPT0E014 exhibited improved cardiac fraction shortening with reducing chamber size. The MPT0E014-treated HF LVs exhibited a smaller increase in the expression of interleukin (IL)-6, p22, SMAD2/3, extracellular signal-regulated kinase 1/2, PPAR isoforms and circulatory tumor growth factor-β1 than the untreated HF LVs did. Moreover, MPT0E014-treated HF LVs expressed less fibroblast growth factor receptor than untreated HF LVs did. Conclusions: HDAC inhibition can improve cardiac function and attenuate the effects of HF on cardiac metabolism and inflammation, which might contribute to the beneficial effects of HDAC inhibition in HF.

Original languageEnglish
Pages (from-to)184-191
Number of pages8
JournalPharmacology
Volume96
Issue number3-4
DOIs
Publication statusPublished - Sep 8 2015

Keywords

  • Fibroblast growth factor
  • Heart failure
  • Histone deacetylase inhibitor
  • Inflammation

ASJC Scopus subject areas

  • Pharmacology

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