| Sort1, encoded by the cardiovascular risk locus 1p13.3, is a regulator of hepatic lipoprotein export. | |
| | |
MedLine Citation:
|
PMID: 20816088 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
|
Recent genome-wide association studies (GWAS) have revealed strong association of hypercholesterolemia and myocardial infarction with SNPs on human chromosome 1p13.3. This locus covers three genes: SORT1, CELSR2, and PSRC1. We demonstrate that sortilin, encoded by SORT1, is an intracellular sorting receptor for apolipoprotein (apo) B100. It interacts with apoB100 in the Golgi and facilitates the formation and hepatic export of apoB100-containing lipoproteins, thereby regulating plasma low-density lipoprotein (LDL) cholesterol. Absence of sortilin in gene-targeted mice reduces secretion of lipoproteins from the liver and ameliorates hypercholesterolemia and atherosclerotic lesion formation in LDL receptor-deficient animals. In contrast, sortilin overexpression stimulates hepatic release of lipoproteins and increases plasma LDL levels. Our data have uncovered a regulatory pathway in hepatic lipoprotein export and suggest a molecular explanation for the cardiovascular risk being associated with 1p13.3. |
| | |
Authors:
|
Mads Kjolby; Olav M Andersen; Tilman Breiderhoff; Anja W Fjorback; Karen Marie Pedersen; Peder Madsen; Pernille Jansen; Joerg Heeren; Thomas E Willnow; Anders Nykjaer |
Related Documents
:
|
3689318 - Plasma lipoprotein and apolipoprotein distribution as a function of density in the rain... 1942468 - Increased lipoprotein x causes hyperlipidemia during intravenous administration of 10% ... 11918278 - Antioxidant enzymes and paraoxonase show a co-activity in preserving low-density lipopr... 172278 - Observations on the passage of apoproteins from plasma lipoproteins into peripheral lym... 16318958 - No significant effect of acute moderate alcohol intake on leptin levels in healthy male... 18662358 - Estimation of the selenium requirement of growing guinea pigs (cavia porcellus). |
Publication Detail:
|
Type: Journal Article; Research Support, Non-U.S. Gov't |
Journal Detail:
|
Title: Cell metabolism Volume: 12 ISSN: 1932-7420 ISO Abbreviation: Cell Metab. Publication Date: 2010 Sep |
Date Detail:
|
Created Date: 2010-09-06 Completed Date: 2010-11-04 Revised Date: - |
Medline Journal Info:
|
Nlm Unique ID: 101233170 Medline TA: Cell Metab Country: United States |
Other Details:
|
Languages: eng Pagination: 213-23 Citation Subset: IM |
Copyright Information:
|
2010 Elsevier Inc. All rights reserved. |
Affiliation:
|
The Lundbeck Foundation Research Center MIND, Department of Medical Biochemistry, Aarhus University, Denmark. |
Export Citation:
|
APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
|
Adaptor Proteins, Vesicular Transport
/
genetics*,
metabolism Animals Apolipoprotein B-100 / metabolism* Biological Transport Cardiovascular Diseases / genetics* Cells, Cultured Chromosomes, Human, Pair 1 / genetics* Diet Genetic Predisposition to Disease Genome-Wide Association Study Humans Hypercholesterolemia / genetics, metabolism Lipoproteins, LDL / blood Liver / cytology, metabolism* Mice Mice, Inbred C57BL Mice, Knockout Receptors, LDL / genetics, metabolism |
| Chemical | |
Reg. No./Substance:
|
0/Adaptor Proteins, Vesicular Transport; 0/Apolipoprotein B-100; 0/Lipoproteins, LDL; 0/Receptors, LDL; 0/sortilin |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
Previous Document: Assembling Complex I with ACAD9.
Next Document: Hepatic-specific disruption of SIRT6 in mice results in fatty liver formation due to enhanced glycol...