Published online before print January 26, 2004, doi: 10.1161/01.CIR.0000109701.77059.E9
(Circulation. 2004;109:544-549.)
© 2004 American Heart Association, Inc.
Basic Science Reports |
Overexpression of Glutathione Peroxidase Prevents Left Ventricular Remodeling and Failure After Myocardial Infarction in Mice
From the Department of Cardiovascular Medicine, Graduate School of Medical Sciences (T.S., H.T., H.M., S.H., M.I., J.W., T.K., A.T.), and Department of Biophysics, Graduate School of Pharmaceutical Sciences (K.M., H.U.), Kyushu University, Fukuoka, Japan.
Correspondence to Hiroyuki Tsutsui, MD, PhD, Department of Cardiovascular Medicine, Graduate School of Medical Sciences, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka, 812-8582, Japan. E-mail prehiro{at}cardiol.med.kyushu-u.ac.jp
Received June 10, 2003; de novo received August 11, 2003; revision received September 23, 2003; accepted September 25, 2003.
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).
Methods and 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.
Key Words: myocardial infarction • heart failure • remodeling • antioxidants • free radicals
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