ArticleThe Journal of biological chemistry2010
Heparan sulfate 2-O-sulfotransferase is required for triglyceride-rich lipoprotein clearance.
Article in The Journal of biological chemistry, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 55 papers, 1 of them a synthesis that pooled it.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
55 citing papers in PubMed, 1 synthesis or guideline pooled it, 80 citations in OpenAlex.
- Meta-analysis identifies gene-by-environment interactions as demonstrated in a study of 4,965 mice.PLoS genetics · 2014Pooled it
- Ext1 heterozygosity causes a modest effect on postprandial lipid clearance in humans.Journal of lipid research · 2015Trial
- Trial
- An RBP-J-heparan sulfate-dependent gatekeeper directs macrophage fate between inflammatory regulation and osteoclastogenesis.bioRxiv : the preprint server for biology · 2026Article
- Epithelial Heparan Sulfate PromotesProteoglycan research · 2025Article
- Heparan sulfate chains in hepatocellular carcinoma.Gastroenterology report · 2025Review
- The Role of Triglyceride-rich Lipoproteins and Their Remnants in Atherosclerotic Cardiovascular Disease.European cardiology · 2023Review
- Chondroitin sulfate enhances the barrier function of basement membrane assembled by heparan sulfate.Development (Cambridge, England) · 2022Article
- Physiology and Pathophysiology of Heparan Sulfate in Animal Models: Its Biosynthesis and Degradation.International journal of molecular sciences · 2022Review
- Role of HSPGs in Systemic Bacterial Infections.Methods in molecular biology (Clifton, N.J.) · 2022Article
- Glycosaminoglycans in Neurodegenerative Diseases.Advances in experimental medicine and biology · 2021Review
- Antiresorptive activity of osteoprotegerin requires an intact heparan sulfate-binding site.Proceedings of the National Academy of Sciences of the United States of America · 2020Article
- Lack of Syndecan-1 produces significant alterations in whole-body composition, metabolism and glucose homeostasis in mice.World journal of diabetes · 2020Article
- Triglyceride-rich lipoprotein binding and uptake by heparan sulfate proteoglycan receptors in a CRISPR/Cas9 library of Hep3B mutants.Glycobiology · 2019Article
- Heparan Sulfate Sulfation by Hs2st Restricts Astroglial Precursor Somal Translocation in Developing Mouse Forebrain by a Non-Cell-Autonomous Mechanism.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2019Article
- Spotlight on the Transglutaminase 2-Heparan Sulfate Interaction.Medical sciences (Basel, Switzerland) · 2019Review
- Effect of Polarization and Chronic Inflammation on Macrophage Expression of Heparan Sulfate Proteoglycans and Biosynthesis Enzymes.The journal of histochemistry and cytochemistry : official journal of the Histochemistry Society · 2019Review
- Integrative Analysis IdentifiedFrontiers in neurology · 2019Article
- A mutant-cell library for systematic analysis of heparan sulfate structure-function relationships.Nature methods · 2018Article
- The heparan sulfate proteoglycan grip on hyperlipidemia and atherosclerosis.Matrix biology : journal of the International Society for Matrix Biology · 2018Review
Corrections and comments
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Authors and funding
13 authors at 3 institutions in 2 countries.
Funding
Abstract
Hepatic clearance of triglyceride-rich lipoproteins depends on heparan sulfate and low density lipoprotein receptors expressed on the basal membrane of hepatocytes. Binding and uptake of the lipoproteins by way of heparan sulfate depends on the degree of sulfation of the chains based on accumulation of plasma triglycerides and delayed clearance of triglyceride-rich lipoproteins in mice bearing a hepatocyte-specific alteration of N-acetylglucosamine (GlcNAc) N-deacetylase-N-sulfotransferase 1 (Ndst1) (MacArthur, J. M., Bishop, J. R., Stanford, K. I., Wang, L., Bensadoun, A., Witztum, J. L., and Esko, J. D. (2007) J. Clin. Invest. 117, 153-164). Inactivation of Ndst1 led to decreased overall sulfation of heparan sulfate due to coupling of uronyl 2-O-sulfation and glucosaminyl 6-O-sulfation to initial N-deacetylation and N-sulfation of GlcNAc residues. To determine whether lipoprotein clearance depends on 2-O-and 6-O-sulfation, we evaluated plasma triglyceride levels in mice containing loxP-flanked conditional alleles of uronyl 2-O-sulfotransferase (Hs2st(f/f)) and glucosaminyl 6-O-sulfotransferase-1 (Hs6st1(f/f)) and the bacterial Cre recombinase expressed in hepatocytes from the rat albumin (Alb) promoter. We show that Hs2st(f/f)AlbCre(+) mice accumulated plasma triglycerides and exhibited delayed clearance of intestinally derived chylomicrons and injected human very low density lipoproteins to the same extent as observed in Ndst1(f/f)AlbCre(+) mice. In contrast, Hs6st1(f/f)AlbCre(+) mice did not exhibit any changes in plasma triglycerides. Chemically modified heparins lacking N-sulfate and 2-O-sulfate groups did not block very low density lipoprotein binding and uptake in isolated hepatocytes, whereas heparin lacking 6-O-sulfate groups was as active as unaltered heparin. Our findings show that plasma lipoprotein clearance depends on specific subclasses of sulfate groups and not on overall charge of the chains.
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Registered trials
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