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 language | English |
|---|---|
| Pages (from-to) | 184-191 |
| Number of pages | 8 |
| Journal | Pharmacology |
| Volume | 96 |
| Issue number | 3-4 |
| DOIs | |
| Publication status | Published - Sep 8 2015 |
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Keywords
- Fibroblast growth factor
- Heart failure
- Histone deacetylase inhibitor
- Inflammation
ASJC Scopus subject areas
- Pharmacology
Cite this
Novel Histone Deacetylase Inhibitor Modulates Cardiac Peroxisome Proliferator-Activated Receptors and Inflammatory Cytokines in Heart Failure. / Lkhagva, Baigalmaa; Lin, Yung Kuo; Kao, Yu Hsun; Chazo, Tze Fan; Chung, Cheng Chih; Chen, Shih Ann; Chen, Yi Jen.
In: Pharmacology, Vol. 96, No. 3-4, 08.09.2015, p. 184-191.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Novel Histone Deacetylase Inhibitor Modulates Cardiac Peroxisome Proliferator-Activated Receptors and Inflammatory Cytokines in Heart Failure
AU - Lkhagva, Baigalmaa
AU - Lin, Yung Kuo
AU - Kao, Yu Hsun
AU - Chazo, Tze Fan
AU - Chung, Cheng Chih
AU - Chen, Shih Ann
AU - Chen, Yi Jen
PY - 2015/9/8
Y1 - 2015/9/8
N2 - 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.
AB - 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.
KW - Fibroblast growth factor
KW - Heart failure
KW - Histone deacetylase inhibitor
KW - Inflammation
UR - http://www.scopus.com/inward/record.url?scp=84940704313&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84940704313&partnerID=8YFLogxK
U2 - 10.1159/000438864
DO - 10.1159/000438864
M3 - Article
C2 - 26304494
AN - SCOPUS:84940704313
VL - 96
SP - 184
EP - 191
JO - Pharmacology
JF - Pharmacology
SN - 0031-7012
IS - 3-4
ER -