Note to users. If you're seeing this message, it means that your browser cannot find this page's style/presentation instructions -- or possibly that you are using a browser that does not support current Web standards. Find out more about why this message is appearing, and what you can do to make your experience of our site the best it can be.

Site Tools

  • AAAS
  • Subscribe
  • Feedback

Site Search

Search Advanced

Science 18 May 2001:
Vol. 292. no. 5520, pp. 1310 - 1312
DOI: 10.1126/science.1061815
Prev | Table of Contents | Next

Perspectives

MOLECULAR MEDICINE:
The Cholesterol Quartet

Joseph L. Goldstein and Michael S. Brown

A high cholesterol diet is known to promote the formation of atherosclerotic plaques in arteries, leading to coronary heart disease. However, there are four monogenic diseases in which plasma cholesterol increases independently of diet due to defects in liver LDL receptors, which fail to clear cholesterol-carrying LDLs from plasma. In a lively and informative Perspective, Brown and Goldstein discuss the newest member of the cholesterol disease quartet, autosomal recessive hypercholesterolemia (ARH), and speculate how mutations in the ARH protein could lead to defective functioning of liver LDL receptors.

The authors are in the Department of Molecular Genetics, University of Texas Southwestern Medical Center, Dallas, TX 75390-9046, USA. E-mail: jgolds@mednet.swmed.edu; mbrow1@mednet.swmed.edu

Read the Full Text


THIS ARTICLE HAS BEEN CITED BY OTHER ARTICLES:
Reduced Apolipoprotein E-Rich High-Density Lipoprotein Level at Birth Is Restored to the Normal Range in Patients with Familial Hypercholesterolemia in the First Year of Life.
H. Nagasaka, T. Miida, K. Hirano, A. Ota, T. Yorifuji, T. Takatani, H. Tsukahara, M. Takayanagi, S.-P. Hui, K. Kobayashi, et al. (2008)
J. Clin. Endocrinol. Metab. 93, 779-783
   Abstract »    Full Text »    PDF »
Purified NPC1 Protein: II. LOCALIZATION OF STEROL BINDING TO A 240-AMINO ACID SOLUBLE LUMINAL LOOP.
R. E. Infante, A. Radhakrishnan, L. Abi-Mosleh, L. N. Kinch, M. L. Wang, N. V. Grishin, J. L. Goldstein, and M. S. Brown (2008)
J. Biol. Chem. 283, 1064-1075
   Abstract »    Full Text »    PDF »
Direct Effect of Cholesterol on Insulin Secretion: A Novel Mechanism for Pancreatic {beta}-Cell Dysfunction.
M. Hao, W. S. Head, S. C. Gunawardana, A. H. Hasty, and D. W. Piston (2007)
Diabetes 56, 2328-2338
   Abstract »    Full Text »    PDF »
LRP6 Mutation in a Family with Early Coronary Disease and Metabolic Risk Factors.
A. Mani, J. Radhakrishnan, H. Wang, A. Mani, M.-A. Mani, C. Nelson-Williams, K. S. Carew, S. Mane, H. Najmabadi, D. Wu, et al. (2007)
Science 315, 1278-1282
   Abstract »    Full Text »    PDF »
Oxidized Low-Density Lipoprotein Correlates Positively With Toll-Like Receptor 2 and Interferon Regulatory Factor-1 and Inversely With Superoxide Dismutase-1 Expression: Studies in Hypercholesterolemic Swine and THP-1 Cells.
P. Holvoet, P. C. Davey, D. De Keyzer, M. Doukoure, E. Deridder, M.-L. Bochaton-Piallat, G. Gabbiani, E. Beaufort, K. Bishay, N. Andrieux, et al. (2006)
Arterioscler. Thromb. Vasc. Biol. 26, 1558-1565
   Abstract »    Full Text »    PDF »
Analytical Performance and Diagnostic Accuracy of Immunometric Assays for the Measurement of Circulating Oxidized LDL.
P. Holvoet, E. Macy, M. Landeloos, D. Jones, J. S. Nancy, F. Van de Werf, and R. P. Tracy (2006)
Clin. Chem. 52, 760-764
   Abstract »    Full Text »    PDF »
Linkage analysis of LDL cholesterol in American Indian populations: the Strong Heart Family Study.
K. E. North, H. H. H. Goring, S. A. Cole, V. P. Diego, L. Almasy, S. Laston, T. Cantu, B. V. Howard, E. T. Lee, L. G. Best, et al. (2006)
J. Lipid Res. 47, 59-66
   Abstract »    Full Text »    PDF »
A Cluster of Metabolic Defects Caused by Mutation in a Mitochondrial tRNA.
F. H. Wilson, A. Hariri, A. Farhi, H. Zhao, K. F. Petersen, H. R. Toka, C. Nelson-Williams, K. M. Raja, M. Kashgarian, G. I. Shulman, et al. (2004)
Science 306, 1190-1194
   Abstract »    Full Text »    PDF »
Genetic Causes of Monogenic Heterozygous Familial Hypercholesterolemia: A HuGE Prevalence Review.
M. A. Austin, C. M. Hutter, R. L. Zimmern, and S. E. Humphries (2004)
Am. J. Epidemiol. 160, 407-420
   Abstract »    Full Text »    PDF »
Familial Hypercholesterolemia, Peripheral Arterial Disease, and Stroke: A HuGE Minireview.
C. M. Hutter, M. A. Austin, and S. E. Humphries (2004)
Am. J. Epidemiol. 160, 430-435
   Abstract »    Full Text »    PDF »
In Vitro and In Vivo Activities of E5700 and ER-119884, Two Novel Orally Active Squalene Synthase Inhibitors, against Trypanosoma cruzi.
J. A. Urbina, J. L. Concepcion, A. Caldera, G. Payares, C. Sanoja, T. Otomo, and H. Hiyoshi (2004)
Antimicrob. Agents Chemother. 48, 2379-2387
   Abstract »    Full Text »    PDF »
Biology of Cardiac Arrhythmias: Ion Channel Protein Trafficking.
B. P. Delisle, B. D. Anson, S. Rajamani, and C. T. January (2004)
Circ. Res. 94, 1418-1428
   Abstract »    Full Text »    PDF »
Genetic contributors to lipoprotein cholesterol levels in an intercross of 129S1/SvImJ and RIIIS/J inbred mice.
M. A. Lyons, R. Korstanje, R. Li, K. A. Walsh, G. A. Churchill, M. C. Carey, and B. Paigen (2004)
Physiol Genomics 17, 114-121
   Abstract »    Full Text »    PDF »
The Metabolic Syndrome, Circulating Oxidized LDL, and Risk of Myocardial Infarction in Well-Functioning Elderly People in the Health, Aging, and Body Composition Cohort.
P. Holvoet, S. B. Kritchevsky, R. P. Tracy, A. Mertens, S. M. Rubin, J. Butler, B. Goodpaster, and T. B. Harris (2004)
Diabetes 53, 1068-1073
   Abstract »    Full Text »    PDF »
Quantitative trait loci that determine lipoprotein cholesterol levels in an intercross of 129S1/SvImJ and CAST/Ei inbred mice.
M. A. Lyons, H. Wittenburg, R. Li, K. A. Walsh, R. Korstanje, G. A. Churchill, M. C. Carey, and B. Paigen (2004)
Physiol Genomics 17, 60-68
   Abstract »    Full Text »    PDF »
LDLs induce fibroblast spreading independently of the LDL receptor via activation of the p38 MAPK pathway.
I. Dobreva, G. Waeber, V. Mooser, R. W. James, and C. Widmann (2003)
J. Lipid Res. 44, 2382-2390
   Abstract »    Full Text »    PDF »
Identification and characterization of LDL receptor gene mutations in hyperlipidemic Chinese.
J.-H. Chang, J.-P. Pan, D.-Y. Tai, A.-C. Huang, P.-H. Li, H.-L. Ho, H.-L. Hsieh, S.-C. Chou, W.-L. Lin, E. Lo, et al. (2003)
J. Lipid Res. 44, 1850-1858
   Abstract »    Full Text »    PDF »
Normal Sorting but Defective Endocytosis of the Low Density Lipoprotein Receptor in Mice with Autosomal Recessive Hypercholesterolemia.
C. Jones, R. E. Hammer, W.-P. Li, J. C. Cohen, H. H. Hobbs, and J. Herz (2003)
J. Biol. Chem. 278, 29024-29030
   Abstract »    Full Text »    PDF »
Association of High Coronary Heart Disease Risk Status With Circulating Oxidized LDL in the Well-Functioning Elderly: Findings From the Health, Aging, and Body Composition Study.
P. Holvoet, T. B. Harris, R. P. Tracy, P. Verhamme, A. B. Newman, S. M. Rubin, E. M. Simonsick, L. H. Colbert, and S. B. Kritchevsky (2003)
Arterioscler. Thromb. Vasc. Biol. 23, 1444-1448
   Abstract »    Full Text »    PDF »
Cardiovascular Disease.
E. G. Nabel (2003)
N. Engl. J. Med. 349, 60-72
   Full Text »    PDF »
Response of obligate heterozygotes for phytosterolemia to a low-fat diet and to a plant sterol ester dietary challenge.
P. O. Kwiterovich Jr., S. C. Chen, D. G. Virgil, A. Schweitzer, D. R. Arnold, and L. E. Kratz (2003)
J. Lipid Res. 44, 1143-1155
   Abstract »    Full Text »    PDF »
Quantitative trait loci that determine lipoprotein cholesterol levels in DBA/2J and CAST/Ei inbred mice,.
M. A. Lyons, H. Wittenburg, R. Li, K. A. Walsh, G. A. Churchill, M. C. Carey, and B. Paigen (2003)
J. Lipid Res. 44, 953-967
   Abstract »    Full Text »    PDF »
Dietary Fats Differentially Modulate the Expression of Lecithin:Cholesterol Acyltransferase, Apoprotein-A1 and Scavenger Receptor B1 in Rats.
W. Hatahet, L. Cole, B. J. Kudchodkar, and T. V. Fungwe (2003)
J. Nutr. 133, 689-694
   Abstract »    Full Text »    PDF »
The Presence of Xenobiotic Transporters in Rat Placenta.
T. M. Leazer and C. D. Klaassen (2003)
Drug Metab. Dispos. 31, 153-167
   Abstract »    Full Text »    PDF »
The autosomal recessive hypercholesterolemia (ARH) protein interfaces directly with the clathrin-coat machinery.
S. K. Mishra, S. C. Watkins, and L. M. Traub (2002)
PNAS 99, 16099-16104
   Abstract »    Full Text »    PDF »
BAREing it all: the adoption of LXR and FXR and their roles in lipid homeostasis.
P. A. Edwards, H. R. Kast, and A. M. Anisfeld (2002)
J. Lipid Res. 43, 2-12
   Abstract »    Full Text »    PDF »
Obstacles facing translational research in academic medical centers.
J. S. POBER, C. S. NEUHAUSER, and J. M. POBER (2001)
FASEB J 15, 2303-2313
   Abstract »    Full Text »    PDF »


ADVERTISEMENT
Click Me!

ADVERTISEMENT
Click Me!

To Advertise     Find Products

Science. ISSN 0036-8075 (print), 1095-9203 (online)