Summary
Low-density lipoprotein (LDL) receptors are demonstrable in cultured fibroblasts from normal subjects but are decreased or absent in cells from patients with heterozygous or homozygous familial hypercholesterolaemia. In vivo receptor-mediated LDL catabolism, determined as the difference between the turnover rates of125I-LDL and131I-LDL coupled with cyclohexanedione, is responsible for approximately one-third of the total catabolism of LDL in normal subjects, but less than one-fifth in heterozygotes and is totally absent in homozygotes. Receptor-mediated catabolism can be stimulated in normal subjects and in heterozygotes by measures that promote bile acid synthesis, namely, administration of anion-exchange resins or creating a partial ileal bypass. Studies in dogs have shown that such measures stimulate the high-affinity binding of LDL by liver cell mebranes. Taken together, these observations suggest the existence of LDL receptors in human liver, the function of which is to maintain cholesterol homeostasis within the hepatocyte during periods of increased demand. Partial or complete absence of such hepatic receptors may play a major role in the pathogenesis of familial hypercholesterolaemia.
Zusammenfassung
LDL-Rezeptoren lassen sich an Fibroblasten von Normalpersonen in der Gewebekultur nachweisen. An Zellen von Patienten mit heterozygoter oder homozygoter familiärer Hypercholesterinämie sind sie jedoch vermindert oder nicht vorhanden. In vivo kann der rezeptorabhängige LDL-Abbau durch die Differenz der Turnover-Raten von125I-LDL und131I-LDL, gekoppelt mit Cyclohexandion, bestimmt werden. Er beträgt bei Normalpersonen etwa ein Drittel des Gesamtabbaues, bei heterozygoten familiären Hypercholesterinämikern jedoch weniger als ein Fünftel. Homozygoten fehlt dieser Abbauweg völlig. Maßnahmen, die die Gallensäuresynthese anregen, wie Gabe von Anionenaustauscherharzen oder partielle Ileum-Bypass Operation, steigern bei Normalpersonen und Heterozygoten den rezeptorabhängigen LDL-Abbau, nicht dagegen bei Homozygoten. Untersuchungen an Hunden konnten zeigen, daß die so induzierte Gallensäureelimination die hochaffine Bindung von LDL durch Leberzellmembranen stimuliert. Diese Zusammenhänge legen die Existenz von LDL-Rezeptoren in der menschlichen Leber nahe, deren Funktion die Aufrechterhaltung der Cholesterin-Homöostase bei erhöhten Cholesterinbedarf ist. Teilweises oder totales Fehlen dieser Leberrezeptoren spielt vermutlich eine wichtige Rolle in der Pathogenese der familiären Hypercholesterinämie.
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Spengel, F.A., Thompson, G.R. Receptor-mediated low-density lipoprotein catabolism. Klin Wochenschr 60, 319–325 (1982). https://doi.org/10.1007/BF01721621
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DOI: https://doi.org/10.1007/BF01721621