title: Myeloperoxidase-generated oxidants modulate left ventricular remodeling but not infarct size after myocardial infarction.
abstract: BACKGROUND
  Inflammation after myocardial infarction (MI) heralds worse left ventricular (LV) function and clinical outcomes. However, whether inflammation affects LV function by extending myonecrosis and/or altering LV remodeling remains unknown. We hypothesized that cytotoxic aldehydes generated during oxidative stress may adversely affect remodeling and infarct size. One theoretical source of reactive aldehydes is oxidation of common alpha-amino acids by myeloperoxidase (MPO) released by leukocytes. However, a role for MPO in formation of aldehydes in vivo and the functional consequences of MPO-generated oxidants in ischemia/reperfusion models of MI have not been established.
  
  
  RESULTS
  In studies with cell types found in vascular tissue, MPO-oxidation products of glycine (formaldehyde) and threonine (acrolein) were the most cytotoxic. Mass spectrometry studies of myocardial tissue from murine models of acute MI (both chronic left anterior descending coronary artery ligation and ischemia/reperfusion injury) confirmed that MPO serves as a major enzymatic source in the generation of these cytotoxic aldehydes. Interestingly, although MPO-null mice experienced 35.1% (P<0.001) less LV dilation and a 52.2% (P<0.0001) improvement in LV function compared with wild-type mice 24 days after ischemia/reperfusion injury, no difference in infarct size between wild-type and MPO-null mice was noted.
  
  
  CONCLUSIONS
  The present data separate inflammatory effects on infarct size and LV remodeling and demonstrate that MPO-generated oxidants do not significantly affect tissue necrosis after MI but rather have a profound adverse effect on LV remodeling and function.
authors.affiliation: Department of Cell Biology, Cleveland Clinic Foundation, Cleveland, OH 44195, USA.
authors.forename: Nikolay
authors.initials: N
authors.lastname: Vasilyev
authors.forename: Timothy
authors.initials: T
authors.lastname: Williams
authors.forename: Marie-Luise
authors.initials: ML
authors.lastname: Brennan
authors.forename: Samuel
authors.initials: S
authors.lastname: Unzek
authors.forename: Xiaorong
authors.initials: X
authors.lastname: Zhou
authors.forename: Jay W
authors.initials: JW
authors.lastname: Heinecke
authors.forename: Douglas R
authors.initials: DR
authors.lastname: Spitz
authors.forename: Eric J
authors.initials: EJ
authors.lastname: Topol
authors.forename: Stanley L
authors.initials: SL
authors.lastname: Hazen
authors.forename: Marc S
authors.initials: MS
authors.lastname: Penn
mesh_terms: D000171:Acrolein / Q000633:toxicity*; D000447:Aldehydes / Q000494:pharmacology; D000818:Animals; D001011:Aorta; D002417:Cattle; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D005557:Formaldehyde / Q000633:toxicity*; D005978:Glutathione / Q000378:metabolism; D019803:Glutathione Disulfide / Q000378:metabolism; D006801:Humans; D006861:Hydrogen Peroxide / Q000494:pharmacology; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000502:physiology*; D009203:Myocardial Infarction / Q000473:pathology*; D009504:Neutrophils / Q000502:physiology; D009195:Peroxidase / Q000378:metabolism*; D011651:Pulmonary Artery / Q000187:drug effects / Q000502:physiology*; D020257:Ventricular Remodeling / Q000187:drug effects / Q000502:physiology*
chemical_list: D000447:Aldehydes; D005557:Formaldehyde; D000171:Acrolein; D006861:Hydrogen Peroxide; D009195:Peroxidase; D005978:Glutathione; C027576:4-hydroxy-2-nonenal; D019803:Glutathione Disulfide