Mitochondrial proteome remodeling in ischemic heart failure

LIFE SCIENCES

卷:101

Article

Liu, Tingting¹  Chen, Le¹  Kim, Eunjung⁵  Tran, Diana⁴  Phinney, Brett S.⁴  Knowlton, Anne A.^1,2,3 

[1] Univ Calif Davis, Cardiovasc Div, Davis, CA 95616 USA

[2] Univ Calif Davis, Dept Pharmacol, Davis, CA 95616 USA

[3] VA Med Ctr Sacramento, Sacramento, CA USA

[4] Univ Calif Davis, Prote Core Facil, Davis, CA 95616 USA

[5] Daejeon Catholic Univ, St Marys Hosp, Taejon, South Korea

关键词: Proteome remodeling;    Mitochondria;    Ischemic heart failure;    NADH dehydrogenase;    Complex I;    NDUFA5;    NDUFV1;    Heart;    Heart failure;    Complex II;    Complex IV;   

DOI  :  10.1016/j.lfs.2014.02.004

来源: Elsevier

【 摘 要 】

Aims: Mitochondrial dysfunction is an important part of the decline in cardiac function in heart failure. We hypothesized for hypothesized that there would be specific abnormalities in mitochondrial function and proteome with the progression of ischemic heart failure (HF). Main methods: We used a high left anterior descending artery (LAD) ligation in 3-4 month old male rats to generate HF. Rats were studied 9 weeks post-ligation. Key findings: Electron microscopy of left ventricle samples showed mitochondrial changes including decreased size, increased number, abnormal distribution, and cristae loss. Mitochondria in ischemic HF exhibited decreased total ATP, impaired mitochondrial respiration, as well as reduced complex I activity. Analysis of LV mitochondrial proteins by mass spectrometry was performed, and 31 differentially expressed proteins (p < 0.05) of more than 500 total proteins were identified. Of these proteins, 15 were up-regulated and 16 were down-regulated in the failing heart. A set of complex I proteins was significantly decreased, consistent with the impairment of complex I activity. There were distinct changes in mitochondrial function and proteome in ischemic HF. Although there were similarities, the distinction between the reported proteomic changed with TAC pressure overload induced HF and ischemic HF in the current study suggested different pathological mechanisms. Significance: Specific changes in mitochondrial protein expression, which correlate with changes in mitochondrial function, have been identified in ischemic HF for the first time. (C) 2014 Elsevier Inc. All rights reserved.

【 授权许可】

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