title: Decreased resistance against in vitro oxidation of LDL from patients with familial defective apolipoprotein B-100.
abstract: Familial defective apolipoprotein B-100 (FDB) is caused by a mutation in the receptor-binding region of apolipoprotein B-100, the structural protein of the low-density lipoprotein (LDL) particle. We studied the effect of this mutation on the composition and susceptibility to oxidative modification of LDL in patients with FDB. Twenty Dutch carriers of the mutation identified in a family study were matched with 20 unaffected siblings of similar age and sex. The mean concentration of LDL cholesterol was 5.19 +/- 0.94 versus 2.9 +/- 0.5 mmol/L in control subjects (P < .0001). Measurement of LDL oxidizability in vitro by continuously monitoring conjugated-diene absorbance showed that LDL from FDB patients was significantly less resistant against oxidation (lag time, 90 +/- 22 minutes versus 108 +/- 21 minutes; P < .05); furthermore, the maximal rate of diene production and total diene production were also significantly increased. Analysis of the chemical composition revealed an increased relative content of cholesteryl esters and reduced content of protein in the LDL of FDB patients (cholesterol-to-protein ratio, 1.54 +/- 0.24 versus 1.25 +/- 0.23; P < .01). The relative amount of arachidonic acid in LDL was increased and that of stearic acid was decreased. The vitamin E (alpha-tocopherol) content per gram of LDL protein was similar to that in control subjects. The relative amount of cholesteryl esters and protein in LDL as well as the fatty acid composition were significantly correlated with LDL oxidizability. Thus, compositional factors in LDL resulting in increased susceptibility to oxidative modification may contribute to the increased risk of premature vascular disease in FDB.
authors.affiliation: Department of Internal Medicine, University Hospital Nijmegen, The Netherlands.
authors.forename: A F
authors.initials: AF
authors.lastname: Stalenhoef
authors.forename: J C
authors.initials: JC
authors.lastname: Defesche
authors.forename: H A
authors.initials: HA
authors.lastname: Kleinveld
authors.forename: P N
authors.initials: PN
authors.lastname: Demacker
authors.forename: J J
authors.initials: JJ
authors.lastname: Kastelein
mesh_terms: D000328:Adult; D053299:Apolipoprotein B-100; D001055:Apolipoproteins B / Q000235:genetics*; D005227:Fatty Acids / Q000032:analysis; D005260:Female; D006801:Humans; D008077:Lipoproteins, LDL / Q000032:analysis / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D009154:Mutation; D010084:Oxidation-Reduction; D014810:Vitamin E / Q000032:analysis
chemical_list: D053299:Apolipoprotein B-100; D001055:Apolipoproteins B; D005227:Fatty Acids; D008077:Lipoproteins, LDL; D014810:Vitamin E