DEFECTIVE LIPOPROTEIN RECEPTORS AND ATHEROSCLEROSIS - LESSONS FROM AN ANIMAL COUNTERPART OF FAMILIAL HYPERCHOLESTEROLEMIA
DEFECTIVE LIPOPROTEIN RECEPTORS AND ATHEROSCLEROSIS - LESSONS FROM AN ANIMAL COUNTERPART OF FAMILIAL HYPERCHOLESTEROLEMIA
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DOI：
10.1056/nejm198308043090507
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发表时间：
1983-01-01
影响因子：
158.5
通讯作者：
BROWN, MS
中科院分区：
文献类型：
--
作者：
GOLDSTEIN, JL;KITA, T;BROWN, MS
研究与一个新的品系的兔子，指定Witanabe遗传性高脂血症（WHHL），描述。在这些兔子中，大量的高胆固醇血症是由单一的遗传缺陷引起的，尽管摄入了无胆固醇的饮食，但仍发生了暴发性动脉粥样硬化。WHHL兔的缺陷在于低密度脂蛋白（LDL）受体基因，与家族性高胆固醇血症患者的缺陷基因相同。WHHL兔与高胆固醇血症患者一样，携带内源性胆固醇的脂蛋白纯粹增加。此外，动脉粥样硬化的模式发展为与人类疾病的模式难以区分。这表明，与WHHL兔的研究已经突出了重要的一部分，LDL受体在肝脏中发挥控制生产和清除的脂蛋白，携带内源性胆固醇和研究结果有影响的动脉粥样硬化的预防和治疗不仅在患者的家族性高胆固醇血症，但也在患者更常见的形式的高胆固醇血症。
Studies with a new strain of rabbits, designated Witanabe heritable hyperlipaemic (WHHL), are described. In those rabbits massive hypercholesterolaemia results from a single genetic defect and fulminant atherosclerosis occurs despite ingestion of a cholesterol-free diet. The defect in WHHL rabbits resides in the gene for the low-density lipoprotein (LDL) receptor, the same gene as that defective in patients with familial hypercholesterolaemia. WHHL rabbits, like patients with hypercholesterolaemia, have a pure increase in lipoproteins which carry endogenous cholesterol. Also, a pattern of atherosclerosis develops which is indistinguishable from the pattern in the human disease. It is suggested that studies with WHHL rabbits have highlighted the important part which LDL receptors in liver play in controlling production and clearance of lipoproteins which carry endogenous cholesterol and that the findings have implications for the prevention and treatment of atherosclerosis not only in patients with familial hypercholesterolaemia but also in patients with more common forms of hypercholesterolaemia.