title: Citrate synthase is a novel in vivo matrix metalloproteinase-9 substrate that regulates mitochondrial function in the postmyocardial infarction left ventricle.
abstract: OBJECTIVE
  To evaluate the role of matrix metalloproteinase (MMP)-9 deletion on citrate synthase (CS) activity postmyocardial infarction (MI).
  
  
  RESULTS
  We fractionated left ventricle (LV) samples using a differential solubility-based approach. The insoluble protein fraction was analyzed by mass spectrometry, and we identified CS as a potential intracellular substrate of MMP-9 in the MI setting. CS protein levels increased in the insoluble fraction at day 1 post-MI in both genotypes (p<0.05) but not in the noninfarcted remote region. The CS activity decreased in the infarcted tissue of wild-type (WT) mice at day 1 post-MI (p<0.05), but this was not observed in the MMP-9 null mice, suggesting that MMP-9 deletion helps to maintain the mitochondrial activity post-MI. Additionally, inflammatory gene transcription was increased post-MI in the WT mice and attenuated in the MMP-9 null mice. MMP-9 cleaved CS in vitro, generating an ∼20 kDa fragment.
  
  
  METHODS
  By applying a sample fractionation and proteomics approach, we were able to identify a novel MMP-9-related altered mitochondrial metabolic activity early post-MI.
  
  
  CONCLUSIONS
  Our data suggest that MMP-9 deletion improves mitochondrial function post-MI.
authors.affiliation: 1 San Antonio Cardiovascular Proteomics Center , San Antonio, Texas.
authors.forename: Lisandra E
authors.initials: LE
authors.lastname: de Castro Brás
authors.forename: Courtney A
authors.initials: CA
authors.lastname: Cates
authors.forename: Kristine Y
authors.initials: KY
authors.lastname: DeLeon-Pennell
authors.forename: Yonggang
authors.initials: Y
authors.lastname: Ma
authors.forename: Rugmani Padmanabhan
authors.initials: RP
authors.lastname: Iyer
authors.forename: Ganesh V
authors.initials: GV
authors.lastname: Halade
authors.forename: Andriy
authors.initials: A
authors.lastname: Yabluchanskiy
authors.forename: Gregg B
authors.initials: GB
authors.lastname: Fields
authors.forename: Susan T
authors.initials: ST
authors.lastname: Weintraub
authors.forename: Merry L
authors.initials: ML
authors.lastname: Lindsey
mesh_terms: D000818:Animals; D002950:Citrate (si)-Synthase / Q000378:metabolism*; D006352:Heart Ventricles / Q000378:metabolism* / Q000473:pathology; D006801:Humans; D020780:Matrix Metalloproteinase 9 / Q000235:genetics* / Q000378:metabolism; D051379:Mice; D018345:Mice, Knockout; D008928:Mitochondria / Q000378:metabolism / Q000473:pathology; D009203:Myocardial Infarction / Q000378:metabolism* / Q000473:pathology
chemical_list: D002950:Citrate (si)-Synthase; D020780:Matrix Metalloproteinase 9