Mitochondrial proteome remodeling in ischemic heart failure

Tingting Liu, Le Chen, Eunjung Kim, Diana Tran, Brett S. Phinney, Anne A Knowlton

Research output: Contribution to journalArticle

20 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)27-36
Number of pages10
JournalLife Sciences
Volume101
Issue number1-2
DOIs
StatePublished - Apr 17 2014

Keywords

  • Complex I
  • Complex II
  • Complex IV
  • Heart
  • Heart failure
  • Ischemic heart failure
  • Mitochondria
  • NADH dehydrogenase
  • NDUFA5
  • NDUFV1
  • Proteome remodeling

ASJC Scopus subject areas

  • Pharmacology, Toxicology and Pharmaceutics(all)
  • Biochemistry, Genetics and Molecular Biology(all)

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