Lipid peroxidation and susceptibility of low-density lipoprotein to in vitro oxidation in hyperhomocysteinaemia.
The pathobiochemical mechanism of arteriosclerosis in hyperhomocysteinaemia has not yet been elucidated. In vitro studies have shown that the cytotoxic properties of homocysteine can be ascribed to its generation 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 comparable age and sex. The susceptibility of low-density lipoprotein (LDL) from hyperhomocysteinaemic patients to oxidation was determined in vitro by continuously measuring the conjugated diene production induced by incubation with copper ions. Oxidation resistance (expressed as lag time), maximal oxidation rate, and extent of oxidation (expressed as total diene production) of LDL from CSD patients were not significantly different from those of LDL from controls. Furthermore, the time needed 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 concentration (+/- SD) of plasma thiobarbituric acid reactive substances (TBARS), an indicator of in vivo lipid peroxidation, was 2.2 +/- 0.7 mumol L-1 in CSD patients, a lower value than that measured in the matched controls (5.0 +/- 2.0 mumol L-1). Investigation of in vivo and in vitro parameters of lipid peroxidation shows that the increased risk of arteriosclerosis in hyperhomocysteinaemia is unlikely to be due to increased lipid peroxidation.
Blom
H J
HJ
Department of Pediatrics, University of Hospital Nijmegen, The Netherlands.
Kleinveld
H A
HA
Boers
G H
GH
Demacker
P N
PN
Hak-Lemmers
H L
HL
Te Poele-Pothoff
M T
MT
Trijbels
J M
JM
D000328:Adult; D000592:Amino Acid Metabolism, Inborn Errors / Q000097:blood* / Q000235:genetics; D002784:Cholesterol / Q000097:blood; D008078:Cholesterol, LDL / Q000097:blood; D015331:Cohort Studies; D005260:Female; D006710:Homocysteine / Q000097:blood / Q000378:metabolism*; D006720:Homozygote; D006801:Humans; D015227:Lipid Peroxidation; D008077:Lipoproteins, LDL / Q000097:blood*; D008297:Male; D008715:Methionine / Q000097:blood; D010084:Oxidation-Reduction; D012016:Reference Values; D017392:Thiobarbituric Acid Reactive Substances / Q000032:analysis; D014810:Vitamin E / Q000097:blood
D008078:Cholesterol, LDL; D008077:Lipoproteins, LDL; D017392:Thiobarbituric Acid Reactive Substances; D006710:Homocysteine; D014810:Vitamin E; D002784:Cholesterol; D008715:Methionine