Characterization of hepatic low density lipoprotein binding and cholesterol metabolism in normal and homozygous familial hypercholesterolemic subjects

Hoeg, JM and Demosky, SJ and Schaefer, EJ and Starzl, TE and Brewer, HB (1984) Characterization of hepatic low density lipoprotein binding and cholesterol metabolism in normal and homozygous familial hypercholesterolemic subjects. Journal of Clinical Investigation, 73 (2). 429 - 436. ISSN 0021-9738

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Abstract

Patients with familial hypercholesterolemia have elevated levels of plasma low density lipoproteins (LDL), increased hepatic synthesis of apolipoprotein B-containing lipoproteins, defective binding of low density lipoproteins to fibroblasts, and premature atherosclerosis. The role of a hepatic low density lipoprotein receptor in normal man and its importance in the pathogenesis of familial hypercholesterolemia have not been previously determined. In the present study, direct comparison was made of the binding of LDL to hepatic membranes from normal and receptor-negative homozygous familial hypercholesterolemic subjects. The effects of calcium, EDTA, and temperature on the binding of lipoproteins to the hepatic membranes were also evaluated. At 4°C, no significant difference in specific binding of LDL to hepatic membranes from normal and familial hypercholesterolemic subjects was observed. At 37°C, both total and specific binding of LDL were significantly reduced in patients with familial hypercholesterolemia. Hepatic membrane binding of LDL from the two patients homozygous for receptor-negative familial hypercholesterolemia was 53 and 59% of normal. The activity of the rate-limiting enzyme in cholesterol biosynthesis, 3-hydroxy-3-methylglutaryl coenzyme A reductase was normal; however, the total hepatic cholesterol and cholesteryl ester content was significantly increased from 53 to 129%. These results indicate that patients with familial hypercholesterolemia have a defect in the interaction of hepatic membranes with low density lipoproteins. This defect may lead to accelerated atherosclerosis by decreasing the cellular catabolism of LDL and enhancing the production of LDL, which is characteristic of patients homozygous for familial hypercholesterolemia.

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Details

Item Type:	Article
Status:	Published
Creators/Authors:	Creators Email Pitt Username ORCID Hoeg, JM Demosky, SJ Schaefer, EJ Starzl, TE tes11@pitt.edu TES11 Brewer, HB
Centers:	Other Centers, Institutes, Offices, or Units > Thomas E. Starzl Transplantation Institute
Date:	1 January 1984
Date Type:	Publication
Journal or Publication Title:	Journal of Clinical Investigation
Volume:	73
Number:	2
Page Range:	429 - 436
DOI or Unique Handle:	10.1172/jci111229
Institution:	University of Pittsburgh
Refereed:	Yes
ISSN:	0021-9738
Other ID:	uls-drl:31735062115351, Starzl CV No. 569
Date Deposited:	08 Apr 2010 17:09
Last Modified:	02 Feb 2019 13:57
URI:	http://d-scholarship.pitt.edu/id/eprint/3955

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