| Heparan sulfate proteoglycans and triglyceride-rich lipoprotein metabolism. | |
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MedLine Citation:
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PMID: 18460924 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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PURPOSE OF REVIEW: Clearance of triglyceride-rich lipoprotein remnants by the liver is a key step in preventing hypertriglyceridemia, an independent risk factor for cardiovascular disease. We review recent genetic evidence that heparan sulfate proteoglycans work in concert with the LDL receptor in the liver to facilitate binding and clearance of both triglyceride and cholesterol-rich lipoproteins from the circulation. RECENT FINDINGS: Partial reduction of sulfation of liver heparan sulfate using the Cre-loxP system caused accumulation of hepatic and dietary triglyceride-rich lipoprotein particles due to delayed clearance. Compounding the mutation with LDL receptor deficiency caused enhanced accumulation of both cholesterol and triglyceride-rich particles compared with mice lacking only LDL receptors. These findings provide the first genetic evidence that hepatic heparan sulfate proteoglycans play a central role in the clearance of lipoproteins by the liver and work independently of LDL receptors. SUMMARY: A role for hepatocyte heparan sulfate in lipoprotein metabolism has now been genetically established in mice. Given this finding, mild, but clinically relevant, hyperlipidemias in human patients may be a result of alterations in heparan sulfate structure or possible genetic polymorphisms in the relevant biosynthetic genes. |
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Authors:
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Joseph R Bishop; Kristin I Stanford; Jeffrey D Esko |
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Publication Detail:
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Type: Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't; Review |
Journal Detail:
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Title: Current opinion in lipidology Volume: 19 ISSN: 0957-9672 ISO Abbreviation: Curr. Opin. Lipidol. Publication Date: 2008 Jun |
Date Detail:
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Created Date: 2008-05-07 Completed Date: 2008-08-05 Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 9010000 Medline TA: Curr Opin Lipidol Country: England |
Other Details:
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Languages: eng Pagination: 307-13 Citation Subset: IM |
Affiliation:
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Department of Cellular and Molecular Medicine, University of California, San Diego, La Jolla, California 92093-0687, USA. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Animals Binding Sites Heparan Sulfate Proteoglycans / metabolism* Humans Lipase / metabolism Lipoproteins / metabolism* Triglycerides / metabolism* |
| Grant Support | |
ID/Acronym/Agency:
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GM33063/GM/NIGMS NIH HHS; HL57345/HL/NHLBI NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/Heparan Sulfate Proteoglycans; 0/Lipoproteins; 0/Triglycerides; EC 3.1.1.3/Lipase |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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