Yang Yuye, Yan Bingyu, Fu Mingde, Xu Yanhua, Tian Ying
Apolipoprotein Research Unit, Department of Biochemistry and Molecular Biology, West China School of Preclinical and Forensic Medicine, Sichuan University, Chengdu, 610041 Sichuan, People's Republic of China.
Clin Chim Acta. 2005 Apr;354(1-2):49-58. doi: 10.1016/j.cccn.2004.11.015. Epub 2004 Dec 24.
It is generally accepted that different high-density lipoprotein (HDL) subclasses have distinct but interrelated metabolic functions. HDL is known to directly influence the atherogenic process and changes in HDL subclasses distribution may be related to the incidence and prevalence of atherosclerosis.
Apo-AI contents(mg/l) of plasma HDL subclasses were determined by 2-dimensional gel electrophoresis coupled with immunodetection for apo-AI. Four hundred forty-two Chinese adults subjects aged 33 to 78 years were assigned to different groups according to the third Report of NCEP (ATP III) guidelines. The subjects were first divided into 2 groups, normal and high TG, then further classified by plasma TC, HDL-C and LDL-C concentrations. The subjects were also divided into TC desirable and TC high groups.
Apo-A contents of prebeta(1)-HDL were higher while HDL(2b) were lower in high TG subjects vs. the corresponding normal TG subjects according to plasma TC and LDL-C concentrations. With the increase of plasma TC concentrations, apo-AI contents of prebeta(1)-HDL were significantly higher in high TC subgroup vs. TC desirable subgroup in normal TG subjects. With the decrease of HDL-C concentrations, apo-AI contents of HDL(2b) tended to decrease in normal TG subjects. And, with the increases of LDL-C concentration, in normal TG subjects, apo-AI contents of prebeta(1)-HDL and HDL(3b) were significantly higher and those of HDL(2b) were significantly lower in very high LDL-C subgroup vs. LDL-C optimal subgroup. On the other hand, apo-AI contents of prebeta(1)-HDL and HDL(3a) were significantly higher, while HDL(2a) and HDL(2b) were significantly lower in high TG and very high TG subgroup vs. normal TG subgroup within either TC desirable or TC high subjects. In a multivariate linear regression model, TG and TC concentrations were all associated independently and positively with high prebeta(1)-HDL; however, HDL-C were inversely associated with high prebeta(1)-HDL. And TG and TC concentrations were all associated independently and negatively with low HDL(2b), but HDL-C and apo-AI were positively associated with low HDL(2b).
With the increase of plasma TG, TC, LDL-C or the decrease of plasma HDL-C concentrations, there was a general shift toward smaller-sized HDL, which, in turn, indicates that reverse cholesterol transport might be weakened and HDL maturation might be abnormal. Plasma TG concentration is a more important factor than TC concentration on the changes of HDL subclass distribution. Moreover, when TG is normal and HDL-C decreased, large-size HDL particles tended to decrease.
普遍认为不同的高密度脂蛋白(HDL)亚类具有独特但相互关联的代谢功能。已知HDL直接影响动脉粥样硬化形成过程,HDL亚类分布的变化可能与动脉粥样硬化的发病率和患病率有关。
采用二维凝胶电泳结合载脂蛋白A-I免疫检测法测定血浆HDL亚类的载脂蛋白A-I含量(mg/l)。根据美国国家胆固醇教育计划(NCEP)第三次报告(ATP III)指南,将442名年龄在33至78岁的中国成年人受试者分为不同组。受试者首先分为两组,即正常甘油三酯组和高甘油三酯组,然后根据血浆总胆固醇(TC)、高密度脂蛋白胆固醇(HDL-C)和低密度脂蛋白胆固醇(LDL-C)浓度进一步分类。受试者还被分为TC理想组和TC高组。
根据血浆TC和LDL-C浓度,高甘油三酯受试者与相应的正常甘油三酯受试者相比,前β(1)-HDL的载脂蛋白A含量较高,而HDL(2b)的载脂蛋白A含量较低。随着血浆TC浓度的升高,正常甘油三酯受试者中高TC亚组的前β(1)-HDL载脂蛋白A-I含量显著高于TC理想亚组。随着HDL-C浓度的降低,正常甘油三酯受试者中HDL(2b)的载脂蛋白A-I含量趋于降低。而且,随着LDL-C浓度的升高,在正常甘油三酯受试者中,极低LDL-C亚组的前β(1)-HDL和HDL(3b)的载脂蛋白A-I含量显著高于LDL-C理想亚组,而HDL(2b)的载脂蛋白A-I含量显著低于LDL-C理想亚组。另一方面,在TC理想或TC高的受试者中,高甘油三酯和极高甘油三酯亚组与正常甘油三酯亚组相比,前β(1)-HDL和HDL(3a)的载脂蛋白A-I含量显著较高,而HDL(2a)和HDL(2b)的载脂蛋白A-I含量显著较低。在多变量线性回归模型中,甘油三酯和总胆固醇浓度均独立且正相关于高前β(1)-HDL;然而,HDL-C与高前β(1)-HDL呈负相关。甘油三酯和总胆固醇浓度均独立且负相关于低HDL(2b),但HDL-C和载脂蛋白A-I与低HDL(2b)呈正相关。
随着血浆甘油三酯、总胆固醇、低密度脂蛋白胆固醇升高或血浆高密度脂蛋白胆固醇降低,HDL总体上倾向于向较小尺寸转变,这反过来表明胆固醇逆向转运可能减弱,HDL成熟可能异常。血浆甘油三酯浓度比总胆固醇浓度对HDL亚类分布变化更重要。此外,当甘油三酯正常而HDL-C降低时,大尺寸HDL颗粒趋于减少。