ArticleJournal of thrombosis and haemostasis : JTH2015
Plasma free fatty acid levels influence Zn(2+) -dependent histidine-rich glycoprotein-heparin interactions via an allosteric switch on serum albumin.
Article in Journal of thrombosis and haemostasis : JTH, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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
28 citing papers in PubMed, 54 citations in OpenAlex.
- Binding properties of marine sulfated glycans to coagulation (co)-factors using surface plasmon resonance spectroscopy.Scientific reports · 2026Article
- Investigating the conformational landscape of human histidine-rich glycoprotein using amide HDX-MS.The Biochemical journal · 2025Article
- Properties of the major ZnChemical communications (Cambridge, England) · 2025Article
- Protein disulfide isomerase cleaves allosteric disulfides in histidine-rich glycoprotein to regulate thrombosis.Nature communications · 2024Article
- Binding and detoxification efficiency of albumin decline after haemodialysis.Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association · 2024Article
- Unlocking the brain's zinc code: implications for cognitive function and disease.Frontiers in biophysics · 2024Article
- ZnInternational journal of molecular sciences · 2023Article
- Proteogenomic Features of the Highly Polymorphic Histidine-rich Glycoprotein Arose Late in Evolution.Molecular & cellular proteomics : MCP · 2023Article
- Structural and biochemical characterisation of CoChemical science · 2023Article
- Investigating Native Metal Ion Binding Sites in Mammalian Histidine-Rich Glycoprotein.Journal of the American Chemical Society · 2023Article
- Unique insertion/deletion polymorphisms within histidine-rich region of histidine-rich glycoprotein in Thoroughbred horses.Scientific reports · 2023Article
- Imaging and clinical predictors of acute constipation in patients with acute ischemic stroke.Frontiers in neuroscience · 2023Article
- Strategies for Therapeutic Amelioration of Aberrant Plasma ZnInternational journal of molecular sciences · 2022Review
- Albumin-mediated extracellular zinc speciation drives cellular zinc uptake.Chemical communications (Cambridge, England) · 2022Article
- Review
- The Interplay between Non-Esterified Fatty Acids and Plasma Zinc and Its Influence on Thrombotic Risk in Obesity and Type 2 Diabetes.International journal of molecular sciences · 2021Review
- Albumin-mediated alteration of plasma zinc speciation by fatty acids modulates blood clotting in type-2 diabetes.Chemical science · 2021Article
- A novel 3D-printed centrifugal ultrafiltration method reveals in vivo glycation of human serum albumin decreases its binding affinity for zinc.Metallomics : integrated biometal science · 2020Article
- Plasmodium falciparum histidine rich protein HRPII inhibits the anti-inflammatory function of antithrombin.Journal of thrombosis and haemostasis : JTH · 2020Article
- Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
4 authors at 2 institutions in 1 country.
Funding
Abstract
backgroundHistidine-rich glycoprotein (HRG) regulates coagulation through its ability to bind and neutralize heparins. HRG associates with Zn(2+) to stimulate HRG-heparin complex formation. Under normal conditions, the majority of plasma Zn(2+) associates with human serum albumin (HSA). However, free fatty acids (FFAs) allosterically disrupt Zn(2+) binding to HSA. Thus, high levels of circulating FFAs, as are associated with diabetes, obesity, and cancer, may increase the proportion of plasma Zn(2+) associated with HRG, contributing to an increased risk of thrombotic disease.
objectivesTo characterize Zn(2+) binding by HRG, examine the influence that FFAs have on Zn(2+) binding by HSA, and establish whether FFA-mediated displacement of Zn(2+) from HSA may influence HRG-heparin complex formation.
methodsZn(2+) binding to HRG and to HSA in the presence of different FFA (myristate) concentrations were examined by isothermal titration calorimetry (ITC) and the formation of HRG-heparin complexes in the presence of different Zn(2+) concentrations by both ITC and ELISA. RESULTS AND
conclusionsWe found that HRG possesses 10 Zn(2+) sites (K' = 1.63 × 10(5) ) and that cumulative binding of FFA to HSA perturbed its ability to bind Zn(2+) . Also Zn(2+) binding was shown to increase the affinity with which HRG interacts with unfractionated heparins, but had no effect on its interaction with low molecular weight heparin (~ 6850 Da). [Correction added on 1 December 2014, after first online publication: In the preceding sentence, "6850 kDa" was corrected to "6850 Da".] Speciation modeling of plasma Zn(2+) based on the data obtained suggests that FFA-mediated displacement of Zn(2+) from serum albumin would be likely to contribute to the development of thrombotic complications in individuals with high plasma FFA levels.
Indexed as
Identifiers
What OpenQuestion holds
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.