ArticleShock (Augusta, Ga.)2017
Circulating Heparan Sulfate Fragments Attenuate Histone-Induced Lung Injury Independently of Histone Binding.
Article in Shock (Augusta, Ga.), 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
What it found
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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
17 citing papers in PubMed, 25 citations in OpenAlex.
- Mechanisms of lung crosstalk with end organs: scientific session V-ReSPIRE 2025.American journal of physiology. Lung cellular and molecular physiology · 2025Review
- The Effects of Heparan Sulfate Infusion on Endothelial and Organ Injury in a Rat Pneumosepsis Model.Journal of clinical medicine · 2023Article
- Using heparan sulfate octadecasaccharide (18-mer) as a multi-target agent to protect against sepsis.Proceedings of the National Academy of Sciences of the United States of America · 2023Article
- Heparan sulfates and heparan sulfate binding proteins in sepsis.Frontiers in molecular biosciences · 2023Review
- Serum level of total histone 3, H3K4me3, and H3K27ac after non-emergent cardiac surgery suggests the persistence of smoldering inflammation at 3 months in an adult population.Clinical epigenetics · 2022Article
- Histone H4 induces heparan sulfate degradation by activating heparanase in chlorine gas-induced acute respiratory distress syndrome.Respiratory research · 2022Article
- The Endothelial Glycocalyx: A Possible Therapeutic Target in Cardiovascular Disorders.Frontiers in cardiovascular medicine · 2022Review
- Endothelial glycocalyx degradation during sepsis: Causes and consequences.Matrix biology plus · 2021Article
- Heparan Sulfate Proteoglycans in Viral Infection and Treatment: A Special Focus on SARS-CoV-2.International journal of molecular sciences · 2021Review
- The neurovascular extracellular matrix in health and disease.Experimental biology and medicine (Maywood, N.J.) · 2021Review
- Potential Use of Anti-Inflammatory Synthetic Heparan Sulfate to Attenuate Liver Damage.Biomedicines · 2020Review
- Beneficial non-anticoagulant mechanisms underlying heparin treatment of COVID-19 patients.EBioMedicine · 2020Review
- Heparin as a therapy for COVID-19: current evidence and future possibilities.American journal of physiology. Lung cellular and molecular physiology · 2020Review
- Enzymatic Synthesis of Chondroitin Sulfate E to Attenuate Bacteria Lipopolysaccharide-Induced Organ Damage.ACS central science · 2020Article
- Circulating heparan sulfate fragments mediate septic cognitive dysfunction.The Journal of clinical investigation · 2019Article
- Alveolar glycocalyces during health and critical illness.Proteoglycan researchArticle
- More than a biomarker: the systemic consequences of heparan sulfate fragments released during endothelial surface layer degradation (2017 Grover Conference Series).Pulmonary circulationArticle
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
6 authors at 2 institutions in 2 countries.
Funding
Abstract
Extracellular histones are cationic damage-associated molecular pattern molecules capable of directly inducing cellular injury via charge-mediated interactions with plasma membranes. Accordingly, histones released into the plasma during critical illness are known to contribute to the onset and propagation of lung injury. Vascular injury (with consequent degradation of the endothelial glycocalyx) simultaneously releases anionic heparan sulfate fragments (hexa- to octasaccharides in size) into the plasma. It is unknown whether this endogenous release of heparan sulfate fragments modulates charge-dependent histone cytotoxicity, or if exogenous heparan sulfate fragments could therapeutically attenuate histone-induced lung injury. Using isothermic calorimetry, we found that extracellular histones only bind to heparan sulfate fragments ≥ 10 saccharides in size, suggesting that glycocalyx-derived heparan sulfate hexa/octasaccharides are incapable of intercepting/neutralizing circulating histones. However, we found that even heparan sulfate fragments incapable of histone binding (e.g., tetrasaccharides) attenuated histone-induced lung injury in vivo, suggesting a direct, size-independent protective effect of heparan sulfate. We found that histones had no effect on human neutrophils ex vivo but exerted toll-like receptor-independent cytotoxicity on human pulmonary microvascular endothelial cells in vitro. This cytotoxicity could be prevented by either the addition of negatively charged (i.e., highly sulfated) heparan sulfate tetrasaccharides (incapable of binding histones) or decasaccharides (capable of binding histones). Taken together, our findings suggest that heparan sulfate oligosaccharides may directly exert pulmonary endothelial-protective effects that attenuate histone-mediated lung injury.
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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.