ArticleThe Journal of clinical investigation2002
Heparin's anti-inflammatory effects require glucosamine 6-O-sulfation and are mediated by blockade of L- and P-selectins.
Article in The Journal of clinical investigation, 2002. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 134 papers, 1 of them a synthesis that pooled it.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
134 citing papers in PubMed, 1 synthesis or guideline pooled it, 316 citations in OpenAlex.
- Heparin for assisted reproduction.The Cochrane database of systematic reviews · 2013Pooled it
- Nebulised heparin for patients with or at risk of acute respiratory distress syndrome: a multicentre, randomised, double-blind, placebo-controlled phase 3 trial.The Lancet. Respiratory medicine · 2021Trial
- Low-molecular-weight-heparin increases Th1- and Th17-associated chemokine levels during pregnancy in women with unexplained recurrent pregnancy loss: a randomised controlled trial.Scientific reports · 2019Trial
- Effects of low molecular weight heparin on the polarization and cytokine profile of macrophages and T helper cells in vitro.Scientific reports · 2018Trial
- Emerging Role, Molecular Mechanisms, and Therapeutic Potential of 2-O, 3-O Desulfated Heparin (ODSH) Across Inflammatory and Vascular Diseases.Antioxidants (Basel, Switzerland) · 2026Review
- Brain vascular stability relies on PAK2-cilia-PDGF-BB-HSPGs on basolateral side of endothelium.Life science alliance · 2026Article
- Safety and efficacy of combined heparin/citrate anticoagulation for cell therapy collections in healthy adult allogeneic donors.Transfusion · 2026Article
- Anticoagulants beyond coagulation: repurposing heparin to mitigate immunothrombosis and inflammatory cascades in sepsis.Frontiers in pharmacology · 2026Review
- Article
- Expanding the Role of Heparin Derivatives in Oncology: From Anticoagulation to Antitumor Activity.Pharmaceuticals (Basel, Switzerland) · 2025Review
- Enzymatic Modulation of the Pulmonary Glycocalyx Enhances Susceptibility toAmerican journal of respiratory cell and molecular biology · 2024Article
- Targeting the P-selectin/PSGL-1 pathway: discovery of disease-modifying therapeutics for disorders of thromboinflammation.Blood vessels, thrombosis & hemostasis · 2024Review
- Exploring the therapeutic role of early heparin administration in ARDS management: a MIMIC-IV database analysis.Journal of intensive care · 2024Article
- Control of tissue homeostasis by the extracellular matrix: Synthetic heparan sulfate as a promising therapeutic for periodontal health and bone regeneration.Periodontology 2000 · 2024Review
- Low Molecular Weight Heparin-Aspirin-Prednisolone Combination Does Not Increase the Live Birth Rate in Recurrent Implantation Failure: A Retrospective Cohort Study.Reproductive sciences (Thousand Oaks, Calif.) · 2023Article
- VSIG4 interaction with heparan sulfates inhibits VSIG4-complement binding.Glycobiology · 2023Article
- Heparan sulfate proteoglycan in Alzheimer's disease: aberrant expression and functions in molecular pathways related to amyloid-β metabolism.American journal of physiology. Cell physiology · 2023Review
- Remodeling articular immune homeostasis with an efferocytosis-informed nanoimitator mitigates rheumatoid arthritis in mice.Nature communications · 2023Article
- Heparin, Heparan Sulphate and Sepsis: Potential New Options for Treatment.Pharmaceuticals (Basel, Switzerland) · 2023Review
- Detection of Glycosaminoglycans in Biological Specimens.Methods in molecular biology (Clifton, N.J.) · 2023Article
74 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
Abstract
Heparin has been used clinically as an anticoagulant and antithrombotic agent for over 60 years. Here we show that the potent anti-inflammatory property of heparin results primarily from blockade of P-selectin and L-selectin. Unfractionated heparin and chemically modified analogs were tested as inhibitors of selectin binding to immobilized sialyl Lewis(X) and of cell adhesion to immobilized selectins or thrombin-activated endothelial cells. Compared with unfractionated heparin, the modified heparinoids had inhibitory activity in this general order: over-O-sulfated heparin > heparin > 2-O,3-O-desulfated > or = N-desulfated/N-acetylated heparin > or = carboxyl-reduced heparin > or= N-,2-O,3-O-desulfated heparin >> 6-O-desulfated heparin. The heparinoids also showed similar differences in their ability to inhibit thioglycollate-induced peritonitis and oxazolone-induced delayed-type hypersensitivity. Mice deficient in P- or L-selectins showed impaired inflammation, which could be further reduced by heparin. However, heparin had no additional effect in mice deficient in both P- and L-selectins. We conclude that (a) heparin's anti-inflammatory effects are mainly mediated by blocking P- and L-selectin-initiated cell adhesion; (b) the sulfate groups at C6 on the glucosamine residues play a critical role in selectin inhibition; and (c) some non-anticoagulant forms of heparin retain anti-inflammatory activity. Such analogs may prove useful as therapeutically effective inhibitors of inflammation.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.