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 L DL particles that have been found to be more prone to oxidative modifi cation. We isolated total LDL as fresh as possible from 12 normolipide mic relatives with a buoyant LDL subfraction profile (group 1), 7 norm olipidemic subjects with a dense LDL subfraction profile (group 2), an d 16 hyperlipidemic FCH subjects with a dense LDL subfraction profile (group 3). In these nonobese and normotensive men, we studied the resi stance of total LDL against Cu2+-oxidation in vitro. In addition, we a nalyzed the alpha-tocopherol and the coenzyme Q10 contents of LDL and determined their relation to LDL oxidizability. LDL isolated from grou p 3 subjects was more susceptible to oxidative modification than LDL f rom 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 polyuns aturated fatty acids in LDL, together with the basal amount of dienes in LDL, were good predictors of the rate of LDL oxidation (R(2)=.73, P =.0001). In groups 2 and 3, the redox status of coenzyme Q10 (ubiquino l-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 meas ure 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 t o oxidation, due to the predominance of dense LDL particles. In additi on, the decreased redox status of coenzyme Q10 in LDL from subjects wi th a dense LDL subfraction profile suggests that the LDL in the circul ation has already undergone some oxidation.