Barbagallo C M, Levine G A, Blanche P J, Ishida B Y, Krauss R M
Life Sciences Division, Ernest Orlando Lawrence Berkeley National Laboratory, University of California, Berkeley 94720, USA.
Arterioscler Thromb Vasc Biol. 1998 Mar;18(3):466-72. doi: 10.1161/01.atv.18.3.466.
We investigated the influence of apolipoprotein (apo) E-containing particles on LDL receptor binding of large, buoyant LDL subfractions (LDL I) from subjects with predominantly large (phenotype A) and small (phenotype B) LDL particles. Direct binding by human fibroblast LDL receptors was tested at 4 degrees C before and after removal of apoE-containing particles by immunoaffinity chromatography. The binding affinity of total LDL I in phenotype B was greater than that in phenotype A (Kd of 1.83+/-0.3 and 3.43+/-0.9 nmol/L, respectively, P<.05). LDL I from phenotype B subjects had a higher apoE to apoB molar ratio than did that from phenotype A (0.16+/-0.04 versus 0.06+/-0.02, P<.05). Nondenaturing gradient gel electrophoresis of apoE-containing LDL I isolated by immunoaffinity chromatography revealed a substantially larger peak particle diameter than in apoE-free LDL I, and comparison of LDL I composition before and after immunoaffinity chromatography suggested an increase in triglyceride content of apoE-containing particles. After removal of these particles, there was a greater than twofold reduction in LDL receptor affinity of phenotype B LDL (Kd of 1.83+/-0.3 to 3.76+/-0.6, P<.01), whereas in phenotype A no change was observed (Kd of 3.43+/-0.9 to 3.57+/-0.4, respectively). The receptor affinity of apoE-free LDL I from phenotype A and B subjects did not differ. These findings confirm that large, buoyant LDL particles from phenotype B subjects have a higher LDL receptor affinity than does LDL I from phenotype A subjects and suggest that this difference is due to an increased content of large, triglyceride-enriched, apoE-containing lipoproteins. It is possible that the accumulation of these particles reflects abnormalities in the metabolism of remnant lipoproteins that contribute to atherosclerosis risk in phenotype B subjects.
我们研究了含载脂蛋白（apo）E颗粒对主要具有大颗粒（A 型表型）和小颗粒（B 型表型）低密度脂蛋白（LDL）的受试者的大的、漂浮性 LDL 亚组分（LDL I）的 LDL 受体结合的影响。在 4℃下，通过免疫亲和色谱法去除含 apoE 颗粒之前和之后，检测人成纤维细胞 LDL 受体的直接结合。B 型表型中总 LDL I 的结合亲和力大于 A 型表型（解离常数分别为 1.83±0.3 和 3.43±0.9 nmol/L，P<0.05）。B 型表型受试者的 LDL I 的 apoE 与 apoB 摩尔比高于 A 型表型（分别为 0.16±0.04 和 0.06±0.02，P<0.05）。通过免疫亲和色谱法分离的含 apoE 的 LDL I 的非变性梯度凝胶电泳显示，其峰值颗粒直径比不含 apoE 的 LDL I 大得多，并且免疫亲和色谱法前后 LDL I 组成的比较表明含 apoE 颗粒的甘油三酯含量增加。去除这些颗粒后，B 型表型 LDL 的 LDL 受体亲和力降低了两倍多（解离常数从 1.83±0.3 变为 3.76±0.6，P<0.01），而 A 型表型未观察到变化（解离常数分别从 3.43±0.9 变为 3.57±0.4）。A 型和 B 型表型受试者的不含 apoE 的 LDL I 的受体亲和力没有差异。这些发现证实，B 型表型受试者的大的、漂浮性 LDL 颗粒比 A 型表型受试者的 LDL I 具有更高的 LDL 受体亲和力，并表明这种差异是由于富含甘油三酯的大的、含 apoE 的脂蛋白含量增加所致。这些颗粒的积累可能反映了残余脂蛋白代谢异常，这导致了 B 型表型受试者的动脉粥样硬化风险。
