Oxidative Stress and Cardiovascular Disease in Type 2 Diabetes: The Role of Antioxidants and Pro-Oxidants

Abstract

Oxidative stress occurs when there is an imbalance between free radical production and antioxidant capacity. This may be due to increased free radical formation in the body and/or loss of normal antioxidant defenses. Oxidative stress has been associated with the development of cardiovascular disease. The role of antioxidants in the primary and secondary prevention of coronary heart disease is currently under study. Although epidemiologic evidence indicates that antioxidants may decrease cardiovascular risk, clinical trial data are not conclusive. Information regarding the use and benefits of antioxidants in persons with diabetes is limited. Persons with diabetes may be more prone to oxidative stress because hyperglycemia depletes natural antioxidants and facilitates the production of free radicals. In addition, other factors such as homocysteine, insulin resistance, and aging may be contributory. This article highlights landmark clinical trials that have examined the cardioprotective effect of antioxidants. Because these trials have not been designed to study persons with diabetes, and clinical trial data for this group are not available, correlational studies are also presented. Finally, the concept of oxidative stress, the antioxidant and pro-oxidant factors that may contribute to oxidative stress, and the consequences of oxidative stress in persons with type 2 diabetes are presented. Key words: antioxidants, clinical trials,

Cardiac overexpression of catalase rescues cardiac contractile dysfunction induced by insulin resistance: role of oxidative stress, protein carbonyl formation and insulin sensitivity

“…Additional evidence suggested that impairment of endothelium-dependent vasodilatation is not a direct consequence of reduced activity/expression of eNOS, but is rather triggered by an enhanced inactivation of nitric oxide by oxidative stress, especially ROS [38]. Oxidative stress and impaired cardiac contractile function have been demonstrated in insulin-resistant states such as type 2 diabetes, hypertension and obesity [1,39]. A highfructose diet has been shown to reduce mRNA expression of antioxidant catalase [40], which itself provides solid support for a therapeutic indication of catalase enzyme.…”

Oxidative stress and its association with coronary artery disease and different atherogenic risk factors

“…In the body exist various antioxidant molecules to be used against free radicals injury. Among them, glutathione and the enzymes superoxide dismutase and glutathione peroxidase are critical for maintaining the redox balance of the cell [6][7]. However, this balance may be destroyed by certain vascular features, such as by certain risk factors for atherosclerosis including hypertension, hyperlipidaemia, diabetes and cigarette smoking [2].…”

“…This is followed by events involved in the atherosclerotic plaque formation such as inflammatory responses, cell proliferation and remodelling of the vasculature and finally to vascular lesion formation, plaque rupture, thrombosis and tissue infarction [1]. A causative relationship exists between these features and oxidative stress in the vessel wall, as pathological events crucial in the onset and progression of vascular disease such as oxidation of LDL, reduction of nitric oxide (NO) bioavailability and vascular inflammation are all modulated by oxidative stress and free radicals generation [2,3].Moreover, to counteract the effect of reactive species, cells are endowed with a complex antioxidant network that operate to prevent or limit oxidant damage [6,7]. In particular, oxidative stress occurs when there is an imbalance between free radical production and antioxidant capacity.…”

Alterations in the diabetic myocardial proteome coupled with increased myocardial oxidative stress underlies diabetic cardiomyopathy

“…It has been reported that increased free-radical mediated oxidative stress is associated with diabetic complications in both humans and animals [4,[12][13][14][15][16]. Reactive Oxygen Species (ROS) or Free Oxygen Radicals (FOR's) such as superoxide radical (O 2 -), hydroxyl radical (OH -), and hydrogen peroxide (H 2 O 2 ), generated during oxygen metabolism, are controlled by various cellular defense mechanisms consisting of enzymatic [(superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GSHPx)] and non-enzymatic (vitamin E, β-carotene, vitamin C) antioxidants [17].…”