ArticleJournal of thrombosis and haemostasis : JTH2023
Glycated albumin modulates the contact system with implications for the kallikrein-kinin and intrinsic coagulation systems.
Article in Journal of thrombosis and haemostasis : JTH, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 4 papers.
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Who cites it
4 citing papers in PubMed, 7 citations in OpenAlex.
- Selective targeting of coagulation factor X Gla domain by negatively charged gold nanoparticles: a novel method for controlled antithrombotic therapy.Materials today. Bio · 2025Article
- Glycation of Proteins and Its End Products: From Initiation to Natural Product-Based Therapeutic Preventions.ACS pharmacology & translational science · 2025Review
- Predicting Preoperative Deep Vein Thrombosis Using d-Dimer-to-Albumin Ratio Combined with Neutrophil-to-Lymphocyte Ratio in Older Patients with Hip Fracture.Clinical interventions in aging · 2025Article
- Next generation anticoagulants: a spotlight on the potential role of activated factors XII and XI.Expert review of hematologyArticle
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Authors and funding
12 authors at 4 institutions in 4 countries.
Funding
Abstract
backgroundHuman serum albumin (HSA) is the most abundant plasma protein and is sensitive to glycation in vivo. The chronic hyperglycemic conditions in patients with diabetes mellitus (DM) induce a nonenzymatic Maillard reaction that denatures plasma proteins and forms advanced glycation end products (AGEs). HSA-AGE is a prevalent misfolded protein in patients with DM and is associated with factor XII activation and downstream proinflammatory kallikrein-kinin system activity without any associated procoagulant activity of the intrinsic pathway.
objectivesThis study aimed to determine the relevance of HSA-AGE toward diabetic pathophysiology.
methodsThe plasma obtained from patients with DM and euglycemic volunteers was probed for activation of FXII, prekallikrein (PK), and cleaved high-molecular-weight kininogen by immunoblotting. Constitutive plasma kallikrein activity was determined via chromogenic assay. Activation and kinetic modulation of FXII, PK, FXI, FIX, and FX via in vitro-generated HSA-AGE were explored using chromogenic assays, plasma-clotting assays, and an in vitro flow model using whole blood.
resultsPlasma obtained from patients with DM contained increased plasma AGEs, activated FXIIa, and resultant cleaved cleaved high-molecular-weight kininogen. Elevated constitutive plasma kallikrein enzymatic activity was identified, which positively correlated with glycated hemoglobin levels, representing the first evidence of this phenomenon. HSA-AGE, generated in vitro, triggered FXIIa-dependent PK activation but limited the intrinsic coagulation pathway activation by inhibiting FXIa and FIXa-dependent FX activation in plasma.
conclusionThese data indicate a proinflammatory role of HSA-AGEs in the pathophysiology of DM via FXII and kallikrein-kinin system activation. A procoagulant effect of FXII activation was lost through the inhibition of FXIa and FIXa-dependent FX activation by HSA-AGEs.
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