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Increased myocardial NAD(P)H oxidase-derived superoxide causes the exacerbation of postinfarct heart failure in type 2 diabetes
| Title: | Increased myocardial NAD(P)H oxidase-derived superoxide causes the exacerbation of postinfarct heart failure in type 2 diabetes |
| Authors: | Matsushima, Shouji Browse this author →KAKEN DB | | Kinugawa, Shintaro Browse this author →KAKEN DB | | Yokota, Takashi Browse this author →KAKEN DB | | Inoue, Naoki Browse this author | | Ohta, Yukihiro Browse this author | | Hamaguchi, Sanae Browse this author | | Tsutsui, Hiroyuki Browse this author →KAKEN DB |
| Keywords: | diabetes | | heart failure | | remodeling | | antioxidants | | free radicals |
| Issue Date: | 2009 |
| Publisher: | American Physiological Society |
| Journal Title: | American Journal of Physiology-Heart and Circulatory Physiology |
| Volume: | 297 |
| Issue: | 1 |
| Start Page: | H409 |
| End Page: | H416 |
| Publisher DOI: | 10.1152/ajpheart.01332.2008 |
| Abstract: | Type 2 diabetes adversely affects the outcomes in patients with myocardial infarction (MI), which is associated with the development of left ventricular (LV) failure. NAD(P)H oxidase-derived superoxide (O2?) production is increased in type 2 diabetes. However, its pathophysiological significance in advanced post-MI LV failure associated with type 2 diabetes remains unestablished. We thus hypothesized that an inhibitor of NAD(P)H oxidase activation, apocynin, could attenuate the exacerbated LV failure after MI in high-fat diet (HFD)-induced obese mice with type 2 diabetes. Male C57BL/6J mice were fed on either HFD or normal diet (ND) for 8 wk. At 4 wk of feeding, MI was created in mice by ligating the left coronary artery. HFD-fed MI mice were treated with either 10 mmol/l apocynin or vehicle. HFD + MI had significantly greater LV end-diastolic diameter (LVEDD; 5.7 ± 0.1 vs. 5.3 ± 0.2 mm), end-diastolic pressure (12 ± 2 vs. 8 ± 1 mmHg), and lung weight/tibial length (10.1 ± 0.3 vs. 8.7 ± 0.7 mg/mm) than ND + MI, which was accompanied by an increased interstitial fibrosis of noninfarcted LV. Treatment of HFD + MI with apocynin significantly decreased LVEDD (5.4 ± 0.1 mm), LV end-diastolic pressure (9.7 ± 0.8 mmHg), lung weight/tibial length (9.0 ± 0.3 mg/mm), and concomitantly interstitial fibrosis of noninfarcted LV to the ND + MI level without affecting body weight, glucose metabolism, and infarct size. NAD(P)H oxidase activity and O2? production were increased in noninfarcted LV tissues from HFD + MI, both of which were attenuated by apocynin to the ND + MI level. Type 2 diabetes was associated with the exacerbation of LV failure after MI via increasing NAD(P)H oxidase-derived O2?, which may be a novel important therapeutic target in advanced heart failure with diabetes. |
| Type: | article |
| URI: | http://hdl.handle.net/2115/76762 |
| 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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