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富含甘油三酯的脂蛋白与受体的相互作用:凝血酶的调节作用。

Interactions of triglyceride-rich lipoproteins with receptors: modulation by thrombin.

作者信息

Gianturco S H, Bradley W A

出版信息

Semin Thromb Hemost. 1986 Oct;12(4):277-9. doi: 10.1055/s-2007-1003566.

DOI:10.1055/s-2007-1003566
PMID:3787267
Abstract

Large VLDL from subjects with HTG but not normal humans bind with high affinity to both the classic LDL receptor present on all cells and the beta-VLDL receptor of macrophages. Binding of HTG-VLDL to the LDL receptor is mediated by a thrombin-accessible conformation of Apo E that is absent in normal VLDL. Binding of HTG VLDL to the beta-VLDL receptor appears to be mediated by one or more apo B species. We find that thrombin-accessible apo E is required for uptake of HTG-VLDL via the LDL receptor but not by the beta-VLDL receptor. Domains within apo B that are present in native chylomicrons and HTG-VLDL or created in vitro with thrombin appear to be required for binding to the beta-VLDL receptor but not the LDL receptor. Triglyceride-rich lipoproteins could be processed in vivo by thrombin or other proteases for preferential uptake and disposal by the beta-VLDL receptor pathway. This process may be involved in the foam cell accumulation and atherosclerosis associated with some types of hypertriglyceridemia.

摘要

来自高甘油三酯血症患者而非正常人的大颗粒极低密度脂蛋白(VLDL)能以高亲和力与所有细胞上存在的经典低密度脂蛋白(LDL)受体以及巨噬细胞的β-VLDL受体结合。高甘油三酯血症性VLDL与LDL受体的结合由凝血酶可及的载脂蛋白E(Apo E)构象介导,而正常VLDL中不存在这种构象。高甘油三酯血症性VLDL与β-VLDL受体的结合似乎由一种或多种载脂蛋白B介导。我们发现,通过LDL受体摄取高甘油三酯血症性VLDL需要凝血酶可及的载脂蛋白E,但通过β-VLDL受体摄取则不需要。天然乳糜微粒和高甘油三酯血症性VLDL中存在的或在体外经凝血酶作用产生的载脂蛋白B结构域似乎是与β-VLDL受体结合所必需的,但与LDL受体结合则不需要。富含甘油三酯的脂蛋白在体内可被凝血酶或其他蛋白酶加工,以便通过β-VLDL受体途径优先摄取和清除。这一过程可能与某些类型的高甘油三酯血症相关的泡沫细胞积聚和动脉粥样硬化有关。

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Interactions of triglyceride-rich lipoproteins with receptors: modulation by thrombin.富含甘油三酯的脂蛋白与受体的相互作用:凝血酶的调节作用。
Semin Thromb Hemost. 1986 Oct;12(4):277-9. doi: 10.1055/s-2007-1003566.
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J Biol Chem. 1986 Aug 25;261(24):11194-201.

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