The redox status of coenzyme Q10 in total LDL as an indicator of in vivo oxidative modification. Studies on subjects with familial combined hyperlipidemia.
Familial combined hyperlipidemia (FCH) is characterized by a familial occurrence of a multiple-type hyperlipidemia, associated with coronary risk. The latter may be related to increased levels of small, dense LDL particles that have been found to be more prone to oxidative modification. We isolated total LDL as fresh as possible from 12 normolipidemic relatives with a buoyant LDL subfraction profile (group 1), 7 normolipidemic subjects with a dense LDL subfraction profile (group 2), and 16 hyperlipidemic FCH subjects with a dense LDL subfraction profile (group 3). In these nonobese and normotensive men, we studied the resistance of total LDL against Cu(2+)-oxidation in vitro. In addition, we analyzed the alpha-tocopherol and the coenzyme Q10 contents of LDL and determined their relation to LDL oxidizability. LDL isolated from group 3 subjects was more susceptible to oxidative modification than LDL from group 1 subjects (lag time: 60.4 +/- 8.1 versus 70.4 +/- 11.4 minutes; P < .05). For the combined groups, the ratio of ubiquinol-10 to polyunsaturated fatty acids in LDL, together with the basal amount of dienes in LDL, were good predictors of the rate of LDL oxidation (R2 = .73, P = .0001). In groups 2 and 3, the redox status of coenzyme Q10 (ubiquinol-10/ubiquinone-10) and the ratio of ubiquinol-10 to alpha-tocopherol in LDL were reduced compared with group 1 (P < .05). The K-value a measure of the LDL density, correlated with the the redox status (r = .37, P < .05). We conclude that in subjects with FCH total LDL is more prone to oxidation, due to the predominance of dense LDL particles. In addition, the decreased redox status of coenzyme Q10 in LDL from subjects with a dense LDL subfraction profile suggests that the LDL in the circulation has already undergone some oxidation.
de Rijke
Y B
YB
Department of Medicine, University Hospital Nijmegen, The Netherlands.
Bredie
S J
SJ
Demacker
P N
PN
Vogelaar
J M
JM
Hak-Lemmers
H L
HL
Stalenhoef
A F
AF
D000328:Adult; D015415:Biomarkers; D003067:Coenzymes; D005190:Family; D005260:Female; D006801:Humans; D006949:Hyperlipidemias / Q000235:genetics / Q000378:metabolism*; D008077:Lipoproteins, LDL / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D010084:Oxidation-Reduction; D014451:Ubiquinone / Q000031:analogs & derivatives* / Q000378:metabolism
D015415:Biomarkers; D003067:Coenzymes; D008077:Lipoproteins, LDL; C099252:oxidized low density lipoprotein; D014451:Ubiquinone; C024989:coenzyme Q10