ArticlePloS one2016
Regulation of Complement and Contact System Activation via C1 Inhibitor Potentiation and Factor XIIa Activity Modulation by Sulfated Glycans - Structure-Activity Relationships.
Article in PloS one, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
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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.
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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
17 citing papers in PubMed, 30 citations in OpenAlex.
- Therapeutic Potential of C1-Inhibitor in Vascular Diseases and Beyond.Arteriosclerosis, thrombosis, and vascular biology · 2026Review
- Sex Differences in Thrombin Generation in Patients with Acute Ischemic Stroke.Translational stroke research · 2025Article
- The Crystal Structure of the Michaelis-Menten Complex of C1 Esterase Inhibitor and C1s Reveals Novel Insights into Complement Regulation.Journal of immunology (Baltimore, Md. : 1950) · 2024Article
- The impact of puberty on the onset, frequency, location, and severity of attacks in hereditary angioedema due to C1-inhibitor deficiency: A survey from the Italian Network for Hereditary and Acquired Angioedema (ITACA).Frontiers in pediatrics · 2023Article
- The Exploration of Complement-Resistance Mechanisms of Pathogenic Gram-Negative Bacteria to Support the Development of Novel Therapeutics.Pathogens (Basel, Switzerland) · 2022Review
- Complement-mediated microvascular injury and thrombosis in the pathogenesis of severe COVID-19: A review.World journal of experimental medicine · 2022Review
- Whole patient knowledge modeling of COVID-19 symptomatology reveals common molecular mechanisms.Frontiers in molecular medicine · 2022Article
- A double edged-sword - The Complement System during SARS-CoV-2 infection.Life sciences · 2021Review
- Cross-Talk between the Complement Pathway and the Contact Activation System of Coagulation: Activated Factor XI Neutralizes Complement Factor H.Journal of immunology (Baltimore, Md. : 1950) · 2021Article
- C1 esterase inhibitor and the contact system in COVID-19.British journal of haematology · 2020Review
- Targeted donor complement blockade after brain death prevents delayed graft function in a nonhuman primate model of kidney transplantation.American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons · 2020Article
- Heparin and non-anticoagulant heparin attenuate histone-induced inflammatory responses in whole blood.PloS one · 2020Article
- Comparison of the Effects of Fucoidans on the Cell Viability of Tumor and Non-Tumor Cell Lines.Marine drugs · 2019Article
- Contradictory to its effects on thrombin, C1-inhibitor reduces plasmin generation in the presence of thrombomodulin.Journal of thrombosis and thrombolysis · 2019Article
- Phycochemical Constituents and Biological Activities ofMarine drugs · 2018Review
- Heparin Mimetics: Their Therapeutic Potential.Pharmaceuticals (Basel, Switzerland) · 2017Review
- Review
Corrections and comments
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Authors and funding
3 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The serpin C1 inhibitor (C1-INH) is the only regulator of classical complement activation as well as the major regulator of the contact system. Its importance is demonstrated by hereditary angioedema (HAE), a severe disease with potentially life-threatening attacks due to deficiency or dysfunction of C1-INH. C1-INH replacement is the therapy of choice in HAE. In addition, C1-INH showed to have beneficial effects in other diseases characterized by inappropriate complement and contact system activation. Due to some limitations of its clinical application, there is a need for improving the efficacy of therapeutically applied C1-INH or to enhance the activity of endogenous C1-INH. Given the known potentiating effect of heparin on C1-INH, sulfated glycans (SG) may be such candidates. The aim of this study was to characterize suitable SG by evaluating structure-activity relationships. For this, more than 40 structurally distinct SG were examined for their effects on C1-INH, C1s and FXIIa. The SG turned out to potentiate the C1s inhibition by C1-INH without any direct influence on C1s. Their potentiating activity proved to depend on their degree of sulfation, molecular mass as well as glycan structure. In contrast, the SG had no effect on the FXIIa inhibition by C1-INH, but structure-dependently modulated the activity of FXIIa. Among the tested SG, β-1,3-glucan sulfates with a Mr ≤ 10 000 were identified as most promising lead candidates for the development of a glycan-based C1-INH amplifier. In conclusion, the obtained information on structural characteristics of SG favoring C1-INH potentiation represent an useful elementary basis for the development of compounds improving the potency of C1-INH in diseases and clinical situations characterized by inappropriate activation of complement and contact system.
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