期刊
INTERNATIONAL JOURNAL OF CARDIOLOGY
卷 168, 期 4, 页码 4178-4183出版社
ELSEVIER IRELAND LTD
DOI: 10.1016/j.ijcard.2013.07.111
关键词
Angiotensin II type I receptor; Fibroblast; Heart failure; Histone deacetylases; Transforming growth factor-beta
资金
- National Science Council, Taiwan [NSC100-2325-B-010-005, NSC101-2325-B-010-005]
- Center of Excellence for Clinical Trial and Research in Neuroscience [DOH101-TD-B-111-003]
- Wan Fang Hospital, Taipei Medical University [102swf08]
Background: Histone deacetylases (HDACs), important epigenetic regulatory enzymes, can reduce cardiac hypertrophy and cardiac fibrosis. However, the mechanisms underlying the antifibrotic activity of HDAC inhibitors remain unclear. The purposes of this study were to evaluate the effects of an HDAC inhibitor on systolic heart failure (HF) and investigate the potential mechanisms. Methods: Echocardiographic, histologic, atrial natriuretic peptide (ANP), and Western blot measurements were performed in HF rats (isoproterenol 100 mg/kg, subcutaneous injection) with and without orally administered (100 mg/kg for 7 consecutive days) MPT0E014 (a novel HDAC inhibitor). Western blot, migration and proliferation assays were carried out on primary isolated cardiac fibroblasts with and without MPT0E014 (0.1 and 1 mu M) for 24 h. Results: MPT0E014-treated HF rats (n = 6) had better fraction shortening (48 +/- 2 vs. 33 +/- 4%, p = 0.006) and smaller left ventricular end diastolic diameter (4.6 +/- 0.2 vs. 5.6 +/- 0.3 mm, p = 0.031) and systolic diameter (2.4 +/- 0.2 vs. 3.9 +/- 0.3 mm, p = 0.006) than HF (n = 7) rats. MPT0E014-treated HF rats had lower ANP, cardiac fibrosis, and angiotensin II type I receptor (AT1R), transforming growth factor (TGF)-beta, and CaMKII delta protein levels compared to HF rats. MPT0E014 (at 1 mu M, but not 0.1 mu M) decreased the migration and proliferation of cardiac fibroblasts. MPT0E014 (0.1 and 1 mu M) decreased expression of the AT1R and TGF-beta. Conclusions: MPT0E014 improved cardiac contractility and attenuated structural remodeling in isoproterenol-induced dilated cardiomyopathy. The direct antifibrotic activity may have contributed to these beneficial effects. (C) 2013 Elsevier Ireland Ltd. All rights reserved.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据