Evidence for enhanced 8-isoprostane plasma levels, as index of oxidative stress in vivo, in patients with coronary artery disease.

Abstract

It is well known that free radicals contribute to endothelial dysfunction and are involved in ageing and in the pathogenesis and development of many cardiovascular diseases, such as atherosclerosis. Measurement of F(2)-isoprostanes has emerged as probably the most reliable approach to assess oxidative stress status in vivo. In particular, 8-isoprostane (8-epiPGF(2alpha)) has been indicated as a marker of antioxidant deficiency and oxidative stress of potential relevance to assess human vascular diseases. To provide evidence for enhanced oxidative stress in coronary artery disease (CAD). Plasma levels of 8-epiPGF(2alpha) (EIA, Cayman Chemicals, Ann Arbor, Michigan, USA) were measured in 51 patients (19 females, 32 males, age: 58.7+/-1.6 years, mean+/-SEM). Subjects included 13 healthy control subjects (group I), and 38 patients underwent coronary angiography; 11 patients without coronary artery atherosclerotic lesions (group II), and 27 with angiographically proven CAD (group III). Plasma levels of 8-epiPGF(2alpha) were 123.2+/-9.5, 314.6+/-40 and 389.6+/-36.2 pg/ml in groups I, II and III respectively (P<0.05 and P<0.001 groups II and III versus group I, respectively). In group III, 8-epiPGF(2alpha) levels increased with the number of affected vessels (324.4+/-47.2 and 408.3+/-44.1 pg/ml for one- and multi-vessel disease, P=0.07 and P<0.001 versus control subjects, respectively). A significant difference in 8-epiPGF(2alpha) levels was observed between patients with and without hypertension (394.2+/-42.7 and 232.7+/-25.1 pg/ml, P<0.01, respectively). In addition, patients with dyslipidaemia presented higher 8-epiPGF(2alpha) levels with respect to non-dyslipidaemic patients (359.1+/-35.6 and 240.3+/-34.3 pg/ml, P<0.05, respectively). A positive relationship was found between age and 8-epiPGF(2alpha) levels (r=0.42, P<0.01) in the whole population. These findings indicate that elevated levels of plasma 8-epiPGF(2alpha) levels are associated with the extent and the severity of coronary artery disease and with the occurrence of different atherogenic risk factors, supporting the hypothesis that the evaluation of oxidative stress may represent an additional prognostic predictor in such events and a potential target of future therapeutic interventions.