| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH |
|
|
|
|||||||
|
|||||||||
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
1 Department of Cardiovascular Medicine, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan
2 Department of Cardiovascular Medicine, Hokkaido University Graduate School of Medicine, Sapporo , Japan
3 Department of Cardiovascular Medicine, Kyushu University, Higashiku, Fukuoka, Japan
* To whom correspondence should be addressed. E-mail: htsutsui{at}med.hokudai.ac.jp.
Oxidative stress plays an important role in the structural and functional abnormalities of diabetic heart. Glutathione peroxidase (GSHPx) is a critical antioxidant enzyme which removes H2O2 both in 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 wild-type littermates (WT+DM). GSHPx activity was higher in the hearts of TG mice compared to WT mice with no significant changes in other antioxidant enzymes. LV thiobarbituric acid-reactive substances measured in TG+DM at 8 weeks 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 msec, P<0.01). The TG+DM values were comparable with those of WT+Control (tau; 7.8±0.2msec). 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.
This article has been cited by other articles:
|
|
 |
|
  J. Li, T. Ichikawa, L. Villacorta, J. S. Janicki, G. L. Brower, M. Yamamoto, and T. Cui Nrf2 Protects Against Maladaptive Cardiac Responses to Hemodynamic Stress Arterioscler Thromb Vasc Biol, November 1, 2009; 29(11): 1843 - 1850. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 T. Yokota, S. Kinugawa, K. Hirabayashi, S. Matsushima, N. Inoue, Y. Ohta, S. Hamaguchi, M. A. Sobirin, T. Ono, T. Suga, et al. Oxidative stress in skeletal muscle impairs mitochondrial respiration and limits exercise capacity in type 2 diabetic mice Am J Physiol Heart Circ Physiol, September 1, 2009; 297(3): H1069 - H1077. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 H. Tsutsui, S. Kinugawa, and S. Matsushima Mitochondrial oxidative stress and dysfunction in myocardial remodelling Cardiovasc Res, February 15, 2009; 81(3): 449 - 456. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. Boudina and E. D. Abel Diabetic Cardiomyopathy Revisited Circulation, June 26, 2007; 115(25): 3213 - 3223. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 W.H. W. Tang, W. Tong, R. W. Troughton, M. G. Martin, K. Shrestha, A. Borowski, S. Jasper, S. L. Hazen, and A. L. Klein Prognostic Value and Echocardiographic Determinants of Plasma Myeloperoxidase Levels in Chronic Heart Failure J. Am. Coll. Cardiol., June 19, 2007; 49(24): 2364 - 2370. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH |
| Visit Other APS Journals Online |
