Elevated peroxidative glutathione redox status in atherosclerotic patients with increased thickness of carotid intima media

Abstract

Background: Atherosclerosis is a chronic inflammatory disease. Accumulated evidences suggest a deep involvement of oxidative damage in the development of atherosclerosis, but little is discussed over the relationship between plasma glutathione redox status as the most important intrinsic antioxidant defensive mechanism and the atherosclerosis.

Methods: A total of 132 patients suspected with atherosclerosis were assigned to three groups by high frequency ultrasonic examination of the carotid artery. With the thickness of intima of the carotid artery as an index of degree of atherosclerosis progression, 56 were included in plaque-forming group (A), 42 in carotid artery intima-thickening group (B), and 34 in normal carotid artery intima-thickness group (C). All patients were subjected to the measurement of plasma glutathione (GSH) (reduced form GSH and oxidized form GSSG), nicotinamide adenine dinucleotide phosphate (NADP) (reduced form NADPH and oxidized form NADP(+)), oxidized low density lipoprotein (oxLDL), and malondialdehyde (MDA). The GSH/GSSG and NADPH/NADP(+) redox potentials were calculated according to the Nernst equation, and their correlation with intima thickness and oxLDL was analyzed.

Results: With the thickening of artery intima (from group C to A), GSH concentration and the ratio of GSH/GSSG gradually reduced, and GSSG and GSH/GSSG redox potential gradually increased (more positive) (P < 0.05). The NADPH and NADPH/NADP(+) redox status also showed similar but milder changes. The products of oxidative stress oxLDL and MDA increased significantly along with the thickening of artery intima (P < 0.05). The analysis of the relationship between GSH/GSSG redox potential, intima thickness, and oxLDL showed positive correlations (P < 0.05). The plasma GSH/GSSG redox status was positively correlated with the intima thickness of the carotid artery and the oxidized injury of LDL. The redox status shifted to oxidizing direction along with the intima thickening and plaque-forming.

Conclusion: Elevated peroxidative glutathione redox status was deeply implicated in atherosclerosis progressing, and it may be a sensitive and reliable index for monitoring oxidative status in atherosclerosis.