Regulation of oxidative stress and cardioprotection in diabetes mellitus

Abstract

Analysis of the Framingham data has shown that the risk of heart failure is increased substantially among diabetic patients, while persons with the metabolic syndrome have an increased risk of both atherosclerosis and diabetes mellitus. Sleep apnea may be related to the metabolic syndrome and systemic inflammation through hypoxia, which might also cause the cardiac remodeling by increased oxidative stress. On the other hand, the renin-angiotensin system is activated in diabetes, and local angiotensin II production may lead to oxidative damage via the angiotensin II type 1 receptor. Basic and clinical data indicate that angiotensin II receptor blockers have the potential to preserve left ventricular function and prevent cardiac remodeling that is exaggerated by oxidative stress in patients with diabetes. Thus, alleviation of oxidative stress might be one possible strategy in the treatment of diabetic patients associated with sleep apnea.

Keywords: Oxidative stress; diabetes mellitus; hypoxia; remodeling.; sleep apnea.

Fig. (1)

Representative macrographs (A, B) and light micrographs (C, D) of hearts from the diabetic rats. The diabetic rats kept under normoxia exhibited nearly normal morphology (A, C). Hypoxia caused cardiac hypertrophy, disarrangement of myofibers, and increased interstitial fibrosis (B, D). original magnification; x 100.

Fig. (2)

Electron micrographs of the left ventricular (LV) myocardium in diabetic rats. In diabetic rats kept under normoxia, mild deformity of mitochondria was observed. Hypoxia induced ballooning and loss of cristae in many mitochondria (arrows). Treatment with angiotensin-II receptor blocker (ARB) preserved the fine structure of the LV myocardium. Reproduced from Inamoto S, Hayashi T, Tazawa N, et al. Angiotensin- II receptor blocker exerts cardioprotection in diabetic rats exposed to hypoxia. Circ J 2006; 70: 787-792.

Fig. (3)

Role of oxidative stress in the progression of cardiovascular diseases accompanied by diabetes mellitus. Diabetes mellitus induced oxidative stress at least partly through NADPH oxidase activation, and consequently accelerated the progression of cardiovascular diseases. In addition, hypoxia might be implicated in the development of diabetes mellitus and production of reactive oxygen species (ROS), associated with the insult to mitochondria in cardiomyocytes by hypoxia itself.

Fig. (4)

Representative scanning (above) and transmission (below) electron micrographs. Compared with normal rats, increased interstitial fibrosis (white arrow) and thickened basement membrane (black arrow) of capillary (Cap) were observed in diabetic (DM) rats. Treatment with angiotensin-II receptor blocker (ARB) suppressed the interstitial fibrosis and preserved the capillary basement membrane thickness. Scale bar=1 µm. Reproduced from Hayashi T, Sohmiya K, Ukimura A, et al. Angiotensin II receptor blockade prevents microangiopathy and preserves diastolic function in the diabetic rat heart. HEART 2003; 89: 1236-42.