Susceptibility of plasma low density lipoprotein to cupric ion-induced peroxidation in patients with variant angina

Department of Internal Medicine, Toyama Medical and Pharmaceutical University, Japan.

OBJECTIVES. The purpose of this study was to investigate the peroxidative susceptibility of plasma low density lipoprotein in patients with active variant angina and to compare it with that in subjects without coronary spasm. BACKGROUND. Oxidized or modified low density lipoprotein can impair endothelium-dependent vasoregulation and has atherogenic properties; it may be related to the genesis of coronary artery spasm by potentiating agonist-induced vasoconstriction. METHODS. The sensitivity of plasma low density lipoprotein for cupric ion (Cu2+)-induced peroxidation was examined. Low density lipoprotein was isolated from plasma in 112 patients: 21 with active variant angina, 18 with inactive variant angina without anginal attacks during the preceding 6 months, 39 with significant organic coronary artery stenoses but without rest angina and 34 control subjects without coronary artery disease. Lipid peroxidation products in low density lipoprotein were assayed as thiobarbituric acid-reactive substances before and after incubation with various concentrations of Cu2+ at 37 degrees C for 24 h. RESULTS. Significantly higher levels of generation of thiobarbituric acid-reactive substances from plasma low density lipoprotein after incubation with Cu2+ were seen in patients with active variant angina than in patients in the other three groups. The dose-response curve of low density lipoprotein peroxidation induced by Cu2+ shifted to the left in this group as compared with the curve in the other three groups. The vitamin E (alphatocopherol) content of low density lipoprotein fraction in these patients was significantly lower than that in the other groups. After > or = 6 months of an angina-free period in five patients with active variant angina, thiobarbituric acid-reactive substances induced by 0.5 mumol/liter Cu2+ in low density lipoprotein were significantly decreased and vitamin E content was significantly increased. CONCLUSIONS. These results indicate that vitamin E-deficient plasma low density lipoprotein in patients with active variant angina is highly susceptible to peroxidative modification.

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