期刊
EUROPEAN JOURNAL OF PHARMACOLOGY
卷 730, 期 -, 页码 140-147出版社
ELSEVIER SCIENCE BV
DOI: 10.1016/j.ejphar.2014.02.037
关键词
Chronic heart failure: small heat shock protein; Mitochondria; Myocardial infarction; Geranylgeranylacetone
资金
- JSPS KAKENHI [23590115]
- Grants-in-Aid for Scientific Research [23590115] Funding Source: KAKEN
The mechanisms underlying mitochondrial impairment in the failing heart are not yet clear. In a previous study, we found that the levels of small heat shock proteins (HSP) such as mitochondrial HSPB1 and HSPB8 in the failing heart following myocardial infarction were decreased. In the present study, to verify the hypothesis that mitochondrial dysfunction in the failing heart is associated with alterations in mitochondrial small heat shock proteins, we examined the effects of geranylgeranylacetone, a heat shock protein inducer, on the cardiac mitochondrial function after myocardial infarction. When hemodynamic parameters of rats with myocardial infarction were measured at the 8th (8 W) week after coronary artery ligation (CAL), the 8 W-CAL showed signs of chronic heart failure concomitant with a reduced mitochondrial oxygen consumption rate. HSPB1 and HSPB8 contents in the mitochonclrial fraction prepared from the failing heart were decreased, suggesting that an attenuation of mitochondrial translocation of HSPB1 and HSPB8 had led to an impairment of mitochondrial energy-producing ability. Geranylgeranylacetone treatment from the 2nd to 8th week after myocardial infarction attenuated the reduction in mitochondrial HSPB1 and HSPB8 contents. Furthermore, the mitochonclrial energy-producing ability and cardiac pump function were preserved by orally administered geranylgeranylacetone during the development of heart failure. These results suggest that the induction of small heat shock proteins in the infarctecl heart by geranylgeranylacetone treatment contributed to the preservation of mitochondrial function, leading to an improvement of cardiac contractile function. (C) 2014 Elsevier B.V. All rights reserved.
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