LIPID-PEROXIDATION AND SUSCEPTIBILITY OF LOW-DENSITY-LIPOPROTEIN TO IN-VITRO OXIDATION IN HYPERHOMOCYSTEINAEMIA

The pathobiochemical mechanism of arteriosclerosis in hyperhomocystein aemia has not yet been elucidated. In vitro studies have shown that th e cytotoxic properties of homocysteine can be ascribed to its generati on of reactive oxygen species. We studied lipid peroxidation, both in vivo and in vitro, in 10 homozygous cystathionine synthase-deficient ( CSD) patients and in a control group of 10 healthy subjects of compara ble age and sex. The susceptibility of low-density lipoprotein (LDL) f rom hyperhomocysteinaemic patients to oxidation was determined in vitr o by continuously measuring the conjugated diene production induced by incubation with copper ions. Oxidation resistance (expressed as lag t ime), maximal oxidation rate, and extent of oxidation (expressed as to tal diene production) of LDL from CSD patients were not significantly different from those of LDL from controls. Furthermore, the time neede d to reach maximal diene production, i.e. t(max), was similar for LDL from patients and controls. In addition, the vitamin E concentrations in LDL of CSD patients and controls were similar. The mean concentrati on (+/- SD) of plasma thiobarbituric acid reactive substances (TEARS), an indicator of in vivo lipid peroxidation, was 2.2 +/- 0.7 mu mol L( -1) in CSD patients, a lower value than that measured in the matched c ontrols (5.0 +/- 2.0 mu mol L(-1)). Investigation of in vivo and in vi tro parameters of lipid peroxidation shows that the increased risk of arteriosclerosis in hyperhomocysteinaemia is unlikely to be due to inc reased lipid peroxidation.