title: Novel Histone Deacetylase Inhibitor Modulates Cardiac Peroxisome Proliferator-Activated Receptors and Inflammatory Cytokines in Heart Failure.
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.
authors: Graduate Institute of Clinical Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan.
authors: Baigalmaa
authors: B
authors: Lkhagva
authors: Yung-Kuo
authors: YK
authors: Lin
authors: Yu-Hsun
authors: YH
authors: Kao
authors: Tze-Fan
authors: TF
authors: Chazo
authors: Cheng-Chih
authors: CC
authors: Chung
authors: Shih-Ann
authors: SA
authors: Chen
authors: Yi-Jen
authors: YJ
authors: Chen
mesh_terms: D000318:Adrenergic beta-Agonists; D000818:Animals; D002478:Cells, Cultured; D016207:Cytokines / Q000378:metabolism*; D006333:Heart Failure / Q000139:chemically induced / Q000201:enzymology / Q000378:metabolism*; D006352:Heart Ventricles / Q000378:metabolism; D056572:Histone Deacetylase Inhibitors / Q000494:pharmacology*; D006655:Histone Deacetylases / Q000378:metabolism; D006877:Hydroxamic Acids / Q000494:pharmacology*; D007211:Indoles / Q000494:pharmacology*; D007527:Isoenzymes / Q000378:metabolism; D007545:Isoproterenol; D008297:Male; D051379:Mice; D009205:Myocarditis / Q000378:metabolism / Q000517:prevention & control; D009206:Myocardium / Q000378:metabolism; D047492:Peroxisome Proliferator-Activated Receptors / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar
chemical_list: C573556:3-(1-benzenesulfonyl-1H-indol-5-yl)-N-hydroxyacrylamide; D000318:Adrenergic beta-Agonists; D016207:Cytokines; D056572:Histone Deacetylase Inhibitors; D006877:Hydroxamic Acids; D007211:Indoles; D007527:Isoenzymes; D047492:Peroxisome Proliferator-Activated Receptors; D006655:Histone Deacetylases; D007545:Isoproterenol