de Rijke Y B, Bredie S J, Demacker P N, Vogelaar J M, Hak-Lemmers H L, Stalenhoef A F
Department of Medicine, University Hospital Nijmegen, The Netherlands.
Arterioscler Thromb Vasc Biol. 1997 Jan;17(1):127-33. doi: 10.1161/01.atv.17.1.127.
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.
家族性混合性高脂血症（FCH）的特征是家族性发生多种类型的高脂血症，并伴有冠心病风险。后者可能与小而密的低密度脂蛋白（LDL）颗粒水平升高有关，已发现这些颗粒更容易发生氧化修饰。我们尽可能新鲜地从12名具有漂浮LDL亚组分谱的血脂正常亲属（第1组）、7名具有致密LDL亚组分谱的血脂正常受试者（第2组）和16名具有致密LDL亚组分谱的高脂血症FCH受试者（第3组）中分离出总LDL。在这些非肥胖和血压正常的男性中，我们研究了总LDL在体外对Cu(2+)氧化的抗性。此外，我们分析了LDL中的α-生育酚和辅酶Q10含量，并确定了它们与LDL氧化能力的关系。从第3组受试者分离出的LDL比第1组受试者的LDL更容易发生氧化修饰（延迟时间：60.4±8.1分钟对70.4±11.4分钟；P<.05）。对于合并组，LDL中泛醇-10与多不饱和脂肪酸的比例，以及LDL中双烯的基础量，是LDL氧化速率的良好预测指标（R2=.73，P=.0001）。与第1组相比，第2组和第3组中LDL的辅酶Q10氧化还原状态（泛醇-10/泛醌-10）以及泛醇-10与α-生育酚的比例降低（P<.05）。K值（LDL密度的一种度量）与氧化还原状态相关（r=.37，P<.05）。我们得出结论，在FCH受试者中，由于致密LDL颗粒占主导地位，总LDL更容易发生氧化。此外，具有致密LDL亚组分谱的受试者LDL中辅酶Q10的氧化还原状态降低，这表明循环中的LDL已经经历了一些氧化。
