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

Abstract

Objective. It is well known that free radicals contribute to endothelial dysfunction and are involved in the pathogenesis and development of cardiovascular diseases, such as atherosclerosis. The aim of this study was to provide evidence for enhanced oxidative stress in coronary artery disease (CAD). Methods. Plasma levels of 8-isoprostane (8-epiPGF 2a ), marker of lipid peroxidation, were measured in 68 subjects (age: 60 ± 2 years, mean ± SEM). Subjects included 30 healthy control subjects and 38 patients with angiographically proven CAD. In addition, the total antioxidant power (PAO) was evaluated in a subgroup (40 subjects, 12 healthy and 28 CAD). Results. Levels of 8-epiPGF 2a increased with the number of affected vessels (one-and multi-vessel disease versus control subjects, P < 0.001) and considering different risk determinants for atherosclerosis (i.e. hypertension, gender, hypercholesterolaemia, P < 0.01). In multivariate regression models the number of affected vessels was independently correlated with 8-epiPGF 2a (P < 0.05). PAO values significantly decreased with increased number of affected vessels (P < 0.05) and in hypertensive patients when compared with those without hypertension (P < 0.05). In multivariate regression models the number of affected vessels resulted an independent determinant for PAO (P < 0.05). Concentration of 8-epiPGF 2a and PAO also correlated with the number of cardiovascular risk factors (P < 0.01 and P ¼ 0.07, respectively). Conclusion. These findings indicate that elevated levels of plasma 8-epiPGF 2a and reduced antioxidant capacity are associated with the extent and the severity of CAD and with the occurrence and number of different atherogenic risk factors. This observation may assist in providing more information as to how oxidative stress may predispose to atherogenesis and suggest attractive therapeutic strategies in the prevention and treatment of cardiovascular disease.Keywords: atherosclerosis, coronary artery disease, isoprostane, oxidative stress, total antioxidant capacity. IntroductionInitial step of atherogenesis is thought to be an injury to the vessel wall resulting in endothelial dysfunction [1]. 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].Recent studies have indicated F2-isoprostanes, end product of lipid peroxidation, as probably the most valid in vivo markers of oxidative stress [4,5].

Elevated Levels of Oxidative Stress as a Prognostic Predictor of Major Adverse Cardiovascular Events in Patients with Coronary Artery Disease

“…Other evidence indicates that thiobarbituric acid reactive substance (TBARS, indicators of lipid peroxidation) levels are correlated with endothelial dysfunction and coronary artery disease 11,12) . Specifically, our previous data indicated associations between d-ROMs, OXY-adsorbent and Oxidative-INDEX and the presence and severity of CAD, and the relationship between these biomarkers of oxidative stress and the extent and number of risk factors, including the presence of diabetes, dyslipidemia, hypertension, and smoking habit, and with inflammatory biomarkers 5,6,[8][9][10][11] . Interestingly, a significant inverse correlation between d-ROMs and OXY-adsorbent tests (r =−0.3, p ≤ 0.01) was also observed in our CAD patient cohort.…”

Mechanisms of H2O2-induced oxidative stress in endothelial cells

“…Nearly 930,000 Americans died from cardiovascular diseases (CVD) in 2001, with coronary heart disease (CHD) accounting for approximately 54% of those deaths (AHA 2004a These statistics suggest that a large majority of patients suffering from cardiovascular disease are likely to have chronic oxidative stress, which is thought to be associated with their diagnosed disease state Prasad et al 2003;Vassalle et al 2004). Oxidative stress and ROS are also thought to be important in the progression of atherosclerosis, due to their role in endothelial cell gene expression (Eyries et al 2004).…”

“…Increased pro-oxidants are associated with vascular disease and are thought to be an important early step in vascular disease development, including atherosclerosis and hypertension Landmesser et al 2003;Vassalle et al 2004). …”

Serum oxidizability potential is associated with age and exercise test results

“…Free radical injury has also been implicated in the pathogenesis, evolution, and progression of heart failure [9,[13][14][15]. Furthermore, with the evolution of heart failure, there is a progressive increase in free radical injury and reduction of antioxidant reserves, which impacts significantly on prognosis.…”