Abstract
The aim of the study was to estimate association of the extent of angiographically proven coronary artery disease (CAD) with plasma 8-isoprostane F2 (8-iso-PGF2α) levels as a reliable marker of lipid peroxidation and serum activity of paraoxonase-1, which demonstrates the ability to protect against lipid oxidation. The study included 105 patients with angiographically documented CAD (CAD+) and 45 patients with negative results of coronary angiography (CAD−). Compared to the control group CAD+ patients were characterized by increased 8-iso-PGF2α levels (P = 0.007) and reduced activity of PON-1 towards paraoxon (PONase, P = 0.002) and phenyl acetate (AREase, P = 0.037). Univariate correlation analysis indicated that 8-iso-PGF2α concentrations were positively associated with the severity of CAD as evaluated by the Gensini score (R = 0.41, P < 0.001) while PONase activity (R = −0.26, P < 0.05) and AREase activity (R = −0.23, P < 0.05) were inversely correlated with CAD severity. PONase activity and 8-iso-PGF2α concentration remained independent determinant of atherosclerosis severity in multiple linear regression after adjusting for age, gender, smoking habits, hypertension, type 2 diabetes, statin therapy, and HDL-C and TAG concentration (β coefficients −0.267; P < 0.05 and 0.368; P < 0.001, resp.). The results suggest that PON-1 activity and 8-iso-PGF2α concentration are associated with the presence and extent of coronary stenosis and may be considered additional markers of coronary artery disease.
Highlights
The mechanisms of the onset and development of atherosclerosis are still not entirely resolved oxidation of lipoproteins seems to be essential to this process [1, 2].Various biomarkers of lipid peroxidation are recently of great interest for highlighting pathological mechanisms, and for clinical applications as biomarkers
Statins were being taken by 90% of patients with confirmed atherosclerosis and by 55% in the group with negative results of angiography
The major finding of our study is the demonstration of decreased activity of PON-1 and increased concentration of 8-iso-prostaglandin F2 in patients with coronary artery disease (CAD) proved by angiography and establishment of the correlation between these factors and the severity of CAD
Summary
The mechanisms of the onset and development of atherosclerosis are still not entirely resolved oxidation of lipoproteins seems to be essential to this process [1, 2].Various biomarkers of lipid peroxidation are recently of great interest for highlighting pathological mechanisms, and for clinical applications as biomarkers. Isoprostanes, 8-iso-prostaglandin F2 (8-iso-PGF2α), are recently indicated as the most valid in vivo lipids peroxidation biomarkers [3, 4] which themselves exert proatherogenic function by means of their vasoconstrictive, platelet-activating, and mitogenic properties [5, 6]. The second biomarker with sustained interest of researchers is the high-density lipoprotein associated enzyme: paraoxonase-1 (PON-1). This enzyme hydrolyzes aromatic carboxylic acid esters, organophosphates, and oxidized phospholipids, simultaneously destroying biologically active lipids in mildly oxidized lipoproteins, protecting them against further oxidation [7, 8]. Genetic deletion of PON-1 in animal models of atherosclerosis is associated with increased oxidation of low-density lipoproteins (LDLs), increased macrophage
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