Oxidized low-density lipoprotein autoantibodies in patients with primary gout: effect of urate-lowering therapy.
ABSTRACT Uric acid is a strong scavenger of reactive oxygen species, which are known to contribute to the development of atherosclerosis, while the incidence of atherosclerotic diseases is rather high in patients with gout. Among the established risk factors for atherosclerosis, oxidized LDL is believed to play a major role in its development and progression. Allopurinol and its active metabolite, oxypurinol, have been suggested to possess an antioxidant ability to scavenge the hydroxyl radical. Therefore, allopurinol may be beneficial in the prevention of LDL oxidation, as well as in the treatment of hyperuricemia. The objective of this work was to determine the degree of LDL oxidation in gout and the effect of allopurinol on LDL oxidation.
Age-matched male patients with primary intercritical gout and healthy male adults were included in the study. The serum concentrations of oxidized LDL autoantibodies and total antioxidant status were measured using an enzyme immunoassay.
Serum concentrations of oxidized LDL autoantibodies were significantly higher in patients with gout than the control subjects (p < 0.05) and were significantly decreased after allopurinol treatment (p < 0.05), but not by benzbromarone treatment, in spite of the similar concentrations of uric acid and total antioxidant status in serum following their separate administration.
Although the exact mechanism remains unclear, increased serum concentrations of oxidized LDL may play a role in the high incidence of coronary artery disease in gout. In addition, allopurinol may be more preferable to benzbromarone for treatment of gout in light of its inhibitory action toward LDL oxidation.
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ABSTRACT: This study was designed to establish the clinical significance of antibodies against oxidized low density lipoprotein (anti-Ox-LDL) titer in atherosclerotic coronary artery disease (CAD). Oxidative modification of LDL, which plays a key role in the development of atherosclerosis, induces immunogenic epitopes in the LDL molecule, and the presence of anti-Ox-LDL has been demonstrated in human sera. Anti-Ox-LDL titer was measured by enzyme-linked immunosorbent assay in 108 patients who had angiographically verified CAD, and 31 patients who had chest pain but no significant CAD, as controls. The anti-Ox-LDL titer was higher (p < 0.01) in patients with multivessel CAD (19.4 +/- 10.1 AcU/ml, n = 68) than in the controls (9.8 +/- 4.1). However, no significant difference was shown between the single-vessel CAD group (15.1 +/- 6.4, n = 40) and the controls, or between the multivessel CAD group and the single-vessel CAD group. The titer was higher in patients with unstable angina (21.5 +/- 11.8 AcU/ml, n = 20, p < 0.01), or in patients with acute myocardial infarction (23.1 +/- 12.0, n = 20, p < 0.01) than in patients with stable-effort angina or old myocardial infarction (12.2 +/- 8.6, n = 68). Multiple logistic regression analysis indicated that the anti-Ox-LDL titer most powerfully discriminated CAD patients from controls (odds ratio [OR]: 1.20, 95% confidence interval [CI]: 1.07-1.33, p = 0.0006) and acute coronary syndrome from chronic CAD (OR: 1.09, 95% CI: 1.04-1.14, p = 0.0008). Serum anti-Ox-LDL titer not only can predict a presence of atherosclerotic CAD but also may be a marker of plaque instability. Low density lipoprotein oxidation may play an important role in the development of plaque instability.Journal of the American College of Cardiology 03/2001; 37(3):775-9. · 14.09 Impact Factor
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ABSTRACT: Xanthine oxidase (XO) has been hypothesized to be a potential source of oxygen-derived free radicals during reperfusion of ischemic myocardium based on the fact that allopurinol, a XO-inhibitor, can reduce reperfusion injury. In this communication we report that both allopurinol and oxypurinol, the principle metabolite of allopurinol, prevent the reperfusion injury in isolated pig heart. However, we found that neither pig heart nor pig blood contain any XO activity. Our study showed a direct free radical scavenging action of these XO-inhibitors during ischemia and reperfusion, as judged by the reduction of free radical signals when compared using an Electron Paramagnetic Resonance Spectrometer. Using a Luminometer, we also confirmed that both allopurinol and oxypurinol can scavenge ClO2, HOCl, and significantly inhibit free radical signals generated by activated neutrophils. These XO-inhibitors, however, failed to scavenge O2. and OH. radicals. Our results suggest that these XO-inhibitors salvaged the ischemic-reperfused myocardium by scavenging free radicals, and not by inhibiting XO in the pig heart.Biochemical and Biophysical Research Communications 11/1987; 148(1):314-9. · 2.41 Impact Factor
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ABSTRACT: Density gradient ultracentrifugation of low density lipoproteins (LDL) from 12 normal subjects showed multiple, distinct isopycnic bands. Densitometric scanning of the gradient tubes revealed that each band could be assigned to one of four density intervals and that the boundaries of these intervals were consistent among all the subjects. Analytic ultracentrifuge flotation (S(f)(0)) rates were assigned to the four density intervals, and there was a strong correlation between peak S(f)(0) rate and peak isopycnic banding position (R(f)) of the LDL in the 12 subjects. The S(f)(0) value corresponding to the boundary between the two most buoyant LDL density subgroups was 7.5. This value is close to that previously demonstrated to define two LDL subdivisions (S(f)(0) 0-7 and S(f)(0) 7-12) that were discriminated by differing concentrations in men and women, and differing statistical relationships with levels of HDL and VLDL in a normal population. Further delineation of distinct subspecies of LDL was afforded by electrophoresis in 2-16% gradient polyacrylamide gels. Densitometric scans of protein-stained gels revealed multiple peaks, and particle diameters were assigned to these peaks using calibration markers. Particles of diameter >/= 280 A included both IDL and Lp(a), the latter defined by pre-beta mobility on agarose electrophoresis and density > 1.050 g/ml. LDL particles with diameters 220-272 A could be grouped into seven size intervals defined by modes in the distribution of gradient gel electrophoretic peaks in LDL from a group of 68 healthy men and women. Particle diameters of the major peaks in each of seven density subfractions decreased with increasing density of the fractions. However, particles within each of the size groups were distributed across a range of densities. Use of a lipid-staining procedure allowed identification of electrophoretic bands in whole plasma which corresponded to those seen in isolated LDL, eliminating the possibility that ultracentrifugation was responsible for formation of the subspecies detected by the gradient gel procedure. The application of density gradient ultracentrifugation and gradient gel electrophoresis provides a means of characterizing LDL from normal humans in terms of multiple distinct subpopulations which may also prove to have differing metabolic and pathologic properties.-Krauss, R. M., and D. J. Burke. Identification of multiple subclasses of plasma low density lipoproteins in normal humans.The Journal of Lipid Research 01/1982; 23(1):97-104. · 4.39 Impact Factor