Increased myocardial NAD(P)H oxidase-derived superoxide causes the exacerbation of postinfarct heart failure in type 2 diabetes

Shoji Matsushima, Shintaro Kinugawa, Takashi Yokota, Naoki Inoue, Yukihiro Ohta, Sanae Hamaguchi, Hiroyuki Tsutsui

Research output: Contribution to journalArticle

33 Citations (Scopus)

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 non-infarcted 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 O 2- 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.

Original languageEnglish
JournalAmerican Journal of Physiology - Heart and Circulatory Physiology
Volume297
Issue number1
DOIs
Publication statusPublished - Jul 1 2009
Externally publishedYes

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NADPH Oxidase
Superoxides
Type 2 Diabetes Mellitus
Heart Failure
Myocardial Infarction
High Fat Diet
Diet
Fibrosis
Blood Pressure
Weights and Measures
Obese Mice
Lung
Inbred C57BL Mouse
Coronary Vessels
Body Weight

All Science Journal Classification (ASJC) codes

  • Physiology
  • Cardiology and Cardiovascular Medicine
  • Physiology (medical)

Cite this

Increased myocardial NAD(P)H oxidase-derived superoxide causes the exacerbation of postinfarct heart failure in type 2 diabetes. / Matsushima, Shoji; Kinugawa, Shintaro; Yokota, Takashi; Inoue, Naoki; Ohta, Yukihiro; Hamaguchi, Sanae; Tsutsui, Hiroyuki.

In: American Journal of Physiology - Heart and Circulatory Physiology, Vol. 297, No. 1, 01.07.2009.

Research output: Contribution to journalArticle

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