title: Mitochondrial proteome remodeling in ischemic heart failure.
abstract: OBJECTIVE
  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).
  
  
  METHODS
  We used a high left anterior descending artery (LAD) ligation in 3-4month old male rats to generate HF. Rats were studied 9weeks post-ligation.
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  Specific changes in mitochondrial protein expression, which correlate with changes in mitochondrial function, have been identified in ischemic HF for the first time.
authors.affiliation: Molecular & Cellular Cardiology, Cardiovascular Division, University of California - Davis, Davis, CA, USA.
authors.forename: Tingting
authors.initials: T
authors.lastname: Liu
authors.affiliation: Molecular & Cellular Cardiology, Cardiovascular Division, University of California - Davis, Davis, CA, USA.
authors.forename: Le
authors.initials: L
authors.lastname: Chen
authors.affiliation: Clinical Research, St. Mary's Hospital of Daejeon Catholic University, Daejeon, Republic of Korea.
authors.forename: Eunjung
authors.initials: E
authors.lastname: Kim
authors.affiliation: Proteomics Core Facility, University of California - Davis, Davis, CA, USA.
authors.forename: Diana
authors.initials: D
authors.lastname: Tran
authors.affiliation: Proteomics Core Facility, University of California - Davis, Davis, CA, USA.
authors.forename: Brett S
authors.initials: BS
authors.lastname: Phinney
authors.affiliation: Molecular & Cellular Cardiology, Cardiovascular Division, University of California - Davis, Davis, CA, USA; Pharmacology Department, University of California - Davis, Davis, CA, USA; VA Medical Center Sacramento, CA, USA. Electronic address: aaknowlton@ucdavis.edu.
authors.forename: Anne A
authors.initials: AA
authors.lastname: Knowlton
mesh_terms: D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D015536:Down-Regulation; D042967:Electron Transport Complex I / Q000378:metabolism; D042963:Electron Transport Complex II / Q000378:metabolism; D003576:Electron Transport Complex IV / Q000378:metabolism; D006333:Heart Failure / Q000150:complications / Q000378:metabolism*; D008297:Male; D008929:Mitochondria, Heart / Q000378:metabolism / Q000648:ultrastructure; D024101:Mitochondrial Proteins / Q000378:metabolism*; D017202:Myocardial Ischemia / Q000150:complications / Q000378:metabolism*; D010101:Oxygen Consumption; D020543:Proteome / Q000378:metabolism*; D051381:Rats; D015398:Signal Transduction; D015854:Up-Regulation
chemical_list: D024101:Mitochondrial Proteins; D020543:Proteome; D000255:Adenosine Triphosphate; D042963:Electron Transport Complex II; D003576:Electron Transport Complex IV; D042967:Electron Transport Complex I
keywords: Complex I; Complex II; Complex IV; Heart; Heart failure; Ischemic heart failure; Mitochondria; NADH dehydrogenase; NDUFA5; NDUFV1; Proteome remodeling