title: Overexpression of glutathione peroxidase prevents left ventricular remodeling and failure after myocardial infarction in mice.
abstract: BACKGROUND
  Oxidative stress plays an important role in the pathophysiology of heart failure. We determined whether the overexpression of glutathione peroxidase (GSHPx) could attenuate left ventricular (LV) remodeling and failure after myocardial infarction (MI).
  
  
  RESULTS
  We created MI in 12- to 16-week-old, male GSHPx transgenic mice (TG+MI) and nontransgenic wild-type littermates (WT+MI) by ligating the left coronary artery. GSHPx activity was increased in the hearts of TG mice, with no significant changes in other antioxidant enzymes. LV concentrations of thiobarbituric acid-reactive substances measured in TG+MI at 4 weeks were significantly lower than those in WT+MI. The survival rate during 4 weeks of MI was significantly higher in TG+MI than in WT+MI, although the infarct size was comparable. LV cavity dilatation and dysfunction were significantly attenuated in TG+MI. LV end-diastolic pressure was increased in WT+MI and reduced in TG+MI. Improvement of LV function in TG+MI was accompanied by a decrease in myocyte hypertrophy, apoptosis, and interstitial fibrosis in the noninfarcted LV. Myocardial matrix metalloproteinase-9 zymographic and protein levels were increased in WT+MI after 3 days but were attenuated in TG+MI.
  
  
  CONCLUSIONS
  Overexpression of GSHPx inhibited LV remodeling and failure after MI. Therapies designed to interfere with oxidative stress might be beneficial to prevent cardiac failure.
authors.affiliation: Department of Cardiovascular Medicine, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.
authors.forename: Tetsuya
authors.initials: T
authors.lastname: Shiomi
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Tsutsui
authors.forename: Hidenori
authors.initials: H
authors.lastname: Matsusaka
authors.forename: Kimiyo
authors.initials: K
authors.lastname: Murakami
authors.forename: Shunji
authors.initials: S
authors.lastname: Hayashidani
authors.forename: Masaki
authors.initials: M
authors.lastname: Ikeuchi
authors.forename: Jing
authors.initials: J
authors.lastname: Wen
authors.forename: Toru
authors.initials: T
authors.lastname: Kubota
authors.forename: Hideo
authors.initials: H
authors.lastname: Utsumi
authors.forename: Akira
authors.initials: A
authors.lastname: Takeshita
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000378:metabolism; D017209:Apoptosis; D002303:Cardiac Output, Low / Q000503:physiopathology / Q000517:prevention & control*; D015870:Gene Expression; D005979:Glutathione Peroxidase / Q000235:genetics / Q000378:metabolism*; D006439:Hemodynamics; D008297:Male; D020782:Matrix Metalloproteinases / Q000378:metabolism; D051379:Mice; D008822:Mice, Transgenic; D009203:Myocardial Infarction / Q000378:metabolism / Q000473:pathology / Q000628:therapy*; D009206:Myocardium / Q000201:enzymology / Q000378:metabolism / Q000473:pathology; D009929:Organ Size; D016019:Survival Analysis; D017392:Thiobarbituric Acid Reactive Substances / Q000032:analysis; D018487:Ventricular Dysfunction, Left / Q000473:pathology / Q000503:physiopathology / Q000517:prevention & control*; D020257:Ventricular Remodeling
chemical_list: D000975:Antioxidants; D017392:Thiobarbituric Acid Reactive Substances; D005979:Glutathione Peroxidase; D020782:Matrix Metalloproteinases