Asztalos B F, Roheim P S, Milani R L, Lefevre M, McNamara J R, Horvath K V, Schaefer E J
Lipid Metabolism Laboratory, Jean Mayer USDA Human Nutrition Center on Aging at Tufts University, Boston, MA 02111, USA.
Arterioscler Thromb Vasc Biol. 2000 Dec;20(12):2670-6. doi: 10.1161/01.atv.20.12.2670.
High density lipoproteins (HDLs) and their subspecies play a role in the development of coronary heart disease (CHD). HDL subpopulations were measured by 2-dimensional nondenaturing gel electrophoresis in 79 male control subjects and 76 male CHD patients to test the hypothesis that greater differences in apolipoprotein (apo)A-I-containing HDL subpopulations would exist between these 2 groups than for traditional lipid levels. In CHD subjects, HDL cholesterol (HDL-C) was lower (-14%, P<0.001), whereas total cholesterol and the low density lipoprotein cholesterol/HDL-C ratio were higher (9% [P:<0.05] and 21% [P:<0.01], respectively) compared with control levels. No significant differences were found for low density lipoprotein cholesterol, triglyceride, and apoA-I levels. In CHD subjects, there were significantly (P:<0.001) lower concentrations of the large lipoprotein (Lp)A-I alpha(1) (-35%), pre-alpha(1) (-50%), pre-alpha(2) (-33%), and pre-alpha(3) (-31%) subpopulations, whereas the concentrations of the small LpA-I/A-II alpha(3) particles were significantly (P:<0.001) higher (20%). Because alpha(1) was decreased more than HDL-C and plasma apoA-I concentrations in CHD subjects, the ratios of HDL-C to alpha(1) and of apoA-I to alpha(1) were significantly (P:<0.001) higher by 36% and 57%, respectively, compared with control values. Subjects with low HDL-C levels (</=35 mg/dL) have different distributions of apoA-I-containing HDL subpopulations than do subjects with normal HDL-C levels (>35 mg/dL). Therefore, we stratified participants according to HDL-C concentrations into low and normal groups. The differences in lipid levels between controls and HDL-C-matched cases substantially decreased; however, the significant differences in HDL subspecies remained. Our research findings support the concept that compared with control subjects, CHD patients not only have HDL deficiency but also have a major rearrangement in the HDL subpopulations with significantly lower alpha(1) and pre-alpha(1-3) (LpA-I) and significantly higher alpha(3) (LpA-I/A-II) particles.
高密度脂蛋白(HDL)及其亚类在冠心病(CHD)的发生发展中起作用。通过二维非变性凝胶电泳对79名男性对照受试者和76名男性CHD患者的HDL亚群进行检测,以验证以下假设:与传统血脂水平相比,这两组之间含载脂蛋白(apo)A-I的HDL亚群差异更大。与对照水平相比,CHD患者的HDL胆固醇(HDL-C)较低(-14%,P<0.001),而总胆固醇以及低密度脂蛋白胆固醇/HDL-C比值较高(分别为9%[P<0.05]和21%[P<0.01])。低密度脂蛋白胆固醇、甘油三酯和apoA-I水平未发现显著差异。在CHD患者中,大脂蛋白(Lp)A-Iα(1)(-35%)、前α(1)(-50%)、前α(2)(-33%)和前α(3)(-31%)亚群的浓度显著降低(P<0.001),而小LpA-I/A-IIα(3)颗粒的浓度显著升高(20%,P<0.001)。由于CHD患者中α(1)的降低幅度大于HDL-C和血浆apoA-I浓度,与对照值相比,HDL-C与α(1)的比值以及apoA-I与α(1)的比值分别显著升高36%和57%(P<0.001)。HDL-C水平低(≤35mg/dL)的受试者与HDL-C水平正常(>35mg/dL)的受试者相比,含apoA-I的HDL亚群分布不同。因此,我们根据HDL-C浓度将参与者分为低水平组和正常水平组。对照组与HDL-C匹配病例之间的血脂水平差异大幅降低;然而,HDL亚类的显著差异仍然存在。我们的研究结果支持以下观点:与对照受试者相比,CHD患者不仅存在HDL缺乏,而且HDL亚群发生了重大重排,α(1)和前α(1-3)(LpA-I)显著降低,α(3)(LpA-I/A-II)颗粒显著升高。