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Overexpression of glutathione peroxidase attenuates myocardial remodeling and preserves diastolic function in diabetic heart
Title: | Overexpression of glutathione peroxidase attenuates myocardial remodeling and preserves diastolic function in diabetic heart |
Authors: | Matsushima, Shouji Browse this author →KAKEN DB | Kinugawa, Shintaro Browse this author →KAKEN DB | Ide, Tomomi Browse this author →KAKEN DB | Matsusaka, Hidenori Browse this author | Inoue, Naoki Browse this author | Ohta, Yukihiro Browse this author | Yokota, Takashi Browse this author →KAKEN DB | Sunagawa, Kenji Browse this author →KAKEN DB | Tsutsui, Hiroyuki Browse this author →KAKEN DB |
Keywords: | oxidative stress | diabetes mellitus | heart failure | antioxidant | hypertrophy | glutathione peroxidase |
Issue Date: | 2006 |
Publisher: | American Physiological Society |
Journal Title: | American Journal of Physiology-Heart and Circulatory Physiology |
Volume: | 291 |
Issue: | 5 |
Start Page: | H2237 |
End Page: | H2245 |
Publisher DOI: | 10.1152/ajpheart.00427.2006 |
Abstract: | Oxidative stress plays an important role in the structural and functional abnormalities of diabetic heart. Glutathione peroxidase (GSHPx) is a critical antioxidant enzyme that removes H2O2 in both the cytosol and mitochondia. We hypothesized that the overexpression of GSHPx gene could attenuate left ventricular (LV) remodeling in diabetes mellitus (DM). We induced DM by injection of streptozotocin (160 mg/kg ip) in male GSHPx transgenic mice (TG+DM) and nontransgenic wildtype littermates (WT+DM). GSHPx activity was higher in the hearts of TG mice compared with WT mice, with no significant changes in other antioxidant enzymes. LV thiobarbituric acid-reactive substances measured in TG+DM at 8 wk were significantly lower than those in WT+DM (58 ± 3 vs. 71 ± 5 nmol/g, P < 0.05). Heart rate and aortic blood pressure were comparable between groups. Systolic function was preserved normal in WT+DM and TG+DM mice. In contrast, diastolic function was impaired in WT+DM and was improved in TG+DM as assessed by the deceleration time of peak velocity of transmitral diastolic flow and the time needed for relaxation of 50% maximal LV pressure to baseline value (tau; 13.5 ± 1.2 vs. 8.9 ± 0.7 ms, P < 0.01). The TG+DM values were comparable with those of WT+Control (tau; 7.8 ± 0.2 ms). Improvement of LV diastolic function was accompanied by the attenuation of myocyte hypertrophy, interstitial fibrosis, and apoptosis. Overexpression of GSHPx gene ameliorated LV remodeling and diastolic dysfunction in DM. Therapies designed to interfere with oxidative stress might be beneficial to prevent cardiac abnormalities in DM. |
Type: | article |
URI: | http://hdl.handle.net/2115/76758 |
Appears in Collections: | 医学院・医学研究院 (Graduate School of Medicine / Faculty of Medicine) > 雑誌発表論文等 (Peer-reviewed Journal Articles, etc)
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