In vivo evidence for reduced binding of low density lipoproteins to receptors as a cause of primary moderate hypercholesterolemia.

The causes of primary moderate hypercholesterolemia are not understood, but some patients have reduced fractional clearance rates (FCRs) for low density lipoproteins (LDL). This could be due to either decreased activity of LDL receptors or to a defect in structure (or composition) of LDL that reduces its affinity for receptors. To distinguish between these causes, simultaneous turnover rates of autologous and normal homologous LDL were determined in 15 patients with primary moderate hypercholesterolemia. In 10, turnover rates of both types of LDL were indistinguishable, which indicated that autologous LDL was cleared as efficiently as normal homologous LDL. In five others, FCRs for autologous LDL were significantly lower than for homologous LDL. Two of the latter five were treated with mevinolin, and although FCRs for both types of LDL rose during treatment, differences in FCRs between the two types of LDL persisted. In these five patients, autologous LDL appeared to be a poor ligand for LDL receptors.

[1]  S. Grundy,et al.  Influence of mevinolin on metabolism of low density lipoproteins in primary moderate hypercholesterolemia. , 1985, Journal of lipid research.

[2]  D. Ledbetter,et al.  The human apolipoprotein B-100 gene: a highly polymorphic gene that maps to the short arm of chromosome 2. , 1985, Biochemical and biophysical research communications.

[3]  J. Opitz,et al.  Familial hypercholesterolemia with "normal" cholesterol in obligate heterozygotes. , 1985, American journal of medical genetics.

[4]  S. Grundy,et al.  Kinetic Mechanisms Determining Variability in Low Density Lipoprotein Levels and Rise with Age , 1985, Arteriosclerosis.

[5]  R. Eddy,et al.  Human apolipoprotein B: structure of carboxyl-terminal domains, sites of gene expression, and chromosomal localization. , 1985, Science.

[6]  A. Motulsky,et al.  A partial cDNA clone for human apolipoprotein B. , 1985, Proceedings of the National Academy of Sciences of the United States of America.

[7]  D. Francis,et al.  Immunoassay for the detection and quantitation of infectious human retrovirus, lymphadenopathy-associated virus (LAV). , 1985, Journal of immunological methods.

[8]  S M Grundy,et al.  Mevinolin and colestipol stimulate receptor-mediated clearance of low density lipoprotein from plasma in familial hypercholesterolemia heterozygotes. , 2004, Proceedings of the National Academy of Sciences of the United States of America.

[9]  S. Grundy,et al.  Increased Low Density Lipoprotein Production Associated with Obesity , 1983, Arteriosclerosis.

[10]  S. Grundy,et al.  Influence of polyunsaturated fats on composition of plasma lipoproteins and apolipoproteins. , 1982, Journal of lipid research.

[11]  R. Mahley,et al.  Human E apoprotein heterogeneity. Cysteine-arginine interchanges in the amino acid sequence of the apo-E isoforms. , 1981, The Journal of biological chemistry.

[12]  D. Jacobs,et al.  Lipoprotein‐Cholesterol Distributions in Selected North American Populations: The Lipid Research Clinics Program Prevalence Study , 1980, Circulation.

[13]  R. Mahley,et al.  Enhanced binding by cultured human fibroblasts of apo-E-containing lipoproteins as compared with low density lipoproteins. , 1978, Biochemistry.

[14]  James V. Beck,et al.  Parameter Estimation in Engineering and Science , 1977 .

[15]  L. Simons,et al.  The metabolism of the apoprotein of plasma low density lipoprotein in familial hyperbetalipoproteinaemia in the homozygous form. , 1975, Atherosclerosis.

[16]  J. Fleiss,et al.  Statistical methods for rates and proportions , 1973 .

[17]  C. Matthews,et al.  The theory of tracer experiments with 131I-labelled plasma proteins. , 1957, Physics in medicine and biology.