Systemic elevations of free radical oxidation products of arachidonic acid are associated with angiographic evidence of coronary artery disease

Abstract

Oxidant stress is widely believed to participate in cardiovascular disease pathogenesis. However, progress in defining appropriate systemic anti-oxidant targetted therapies has been hindered by uncertainty in defining clinically relevant systemic oxidant stress measures. In a case control study, 50 subjects with CAD (> 50% stenosis in one or more major coronary vessels) and 54 without CAD (< 30% stenosis in all major coronary vessels) were tested. Plasma was isolated and stored under conditions designed to prevent artificial lipid peroxidation. Systemic levels of multiple (n=9) specific fatty acid oxidation products including individual hydroxy-octadecadienoic acids (HODEs), hydroxy-eicosatetraenoic acids (HETEs), and F 2 -Isoprostanes, were simultaneously measured by high performance liquid chromatography (HPLC) with on-line tandem mass spectrometry, along with traditional risk factors and C-reactive protein (CRP) levels. Of the markers monitored, only 9-HETE and F 2 -Isoprostanes, both products of free radical-mediated arachidonic acid oxidation, were significantly elevated in patients with angiographically defined CAD (9-HETE, 8.7 ± 4 vs. 6.8 ± 4 umol/mol arachidonate, p = 0.011; and F 2 -Isoprostanes, 9.4 ± 5 vs. 6.2 ± 3umol/mol arachidonate, p < 0.001). In multivariable analyses with simultaneous adjustment for Framingham Risk Score and C-reactive protein, 9-HETE (4 th quartile OR=4.8, 95% CI=1.3 to 17.1; P = 0.016) and F 2 -Isoprostanes (4 th quartile OR=9.7, 95% CI=2.56 to 36.9; P < 0.001) remained strong and independent predictors of CAD risk. Systemic levels of 9-HETE and F 2 -Isoprostanes are independently associated with angiographic evidence of CAD and appear superior to other specific oxidation products of arachidonic and linoleic acids as predictors of the presence of angiographically evident coronary artery disease.

Plasma fatty acids, oxylipins, and risk of myocardial infarction: the Singapore Chinese Health Study

“…In a study of human carotid atherosclerotic plaques, the concentration of HETEs was significantly higher in symptomatic plaques, as compared with asymptomatic plaques (11). In addition, higher plasma HETE concentrations were associated with CHD in two case-control studies (12,13). However, data from larger prospective studies with a more comprehensive assessment of oxylipins are currently not available.…”

Altered vitamin E status in Niemann-Pick type C disease

“…Since analysis of the NPC-affected tissue is impractical, a sensitive circulating indicator of oxidative stress may be the appropriate biomarker in this case. Circulating unsaturated lipid peroxidation products, such as HETEs and isoprostanes ( 88,89 ), and hydroxylated cholesterol metabolites ( 85 ) may serve as the proper biomarker for these purposes. Clearly, there is a dire need to better defi ne and optimize the most suitable plasma marker for oxidation status and to streamline its applicability for routine clinical use.…”

Impaired Fasting Glucose & 8-Iso-Prostaglandin F2α in Diabetes Disease Progression

“…Isoprostanes, including 8-iso-PGF 2α are stable in biological fluids and easily detectable as well as not being affected by diet and modulated by endogenous antioxidants [30]. Plasma levels of 8-iso-PGF 2α have been associated with atherosclerosis and coronary artery disease as well as DMT2 [31][32][33]. In contrast to crosssectional studies where 8-iso-PGF 2α have been shown to be increased in type 2 diabetes, longitudinal studies have shown an inverse relationship between the level of 8-iso-PGF2α and risk of diabetes independent of traditional risk factors [33,34].…”