Plasma fibrin clot proteomics in healthy subjects: Relation to clot permeability and lysis time

• Published in: Journal of proteomics Vol. 208; p. 103487
• Main Authors: Ząbczyk, Michał, Stachowicz, Aneta, Natorska, Joanna, Olszanecki, Rafał, Wiśniewski, Jacek R., Undas, Anetta
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 30.09.2019
• Subjects: apolipoproteins; body mass index; chemokine CXCL4; Clot; Clot properties; coagulation; complement; Fibrin; fibrinogen; fibronectins; glycoproteins; liquid chromatography; permeability; plasminogen; protein content; protein-glutamine gamma-glutamyltransferase; Proteomics; thrombin; Fibrin; Clot properties; Clot; Proteomics
• ISSN: 1874-3919; 1876-7737
• DOI: 10.1016/j.jprot.2019.103487

Little is known about fibrin clot composition in relation to its structure and lysability. We investigated plasma clots protein composition and its associations with clot properties. We studied 20 healthy subjects aged 31–49 years in whom plasma fibrin clot permeability (Ks) and clot lysis time (CLT) were determined. A proteomic analysis of plasma fibrin clots was based on quantitative liquid chromatography-mass spectrometry. Among 494 clot-bound proteins identified in all clots, the highest concentrations were for fibrinogen chains (about 64% of the clot mass) and fibronectin (13%). α2-antiplasmin (2.7%), factor XIIIA (1.2%), complement component C3 (1.2%), and histidine-rich glycoprotein (HRG, 0.61%) were present at relatively high concentrations. Proteins present in concentrations <0.5% included (pro)thrombin, plasminogen, apolipoproteins, or platelet factor 4 (PF4). Fibrinogen-α and -γ chains were associated with age, while body-mass index with clot-bound apolipoproteins (all p < .05). Ks correlated with fibrinogen-γ and PF4 amounts within plasma clots. CLT was associated with fibrinogen-α and -γ, PF4, and HRG (all p < .05). This study is the first to show associations of two key measures of clot properties with protein content within plasma clots, suggesting that looser fibrin clots with enhanced lysability contain less fibrinogen-γ chain, platelet-derived PF4, and HRG. Our study for the first time suggests that more permeable fibrin clots with enhanced lysability contain less fibrinogen-γ chain, platelet-derived factor 4, and histidine-rich glycoprotein, which is related to accelerated clot lysis. The current findings might have functional consequences regarding clot structure, stability, and propagation of thrombin generation, and detailed proteomic analysis of clots in various disorders opens new perspective for coagulation and fibrin research. [Display omitted] •Unfavorable fibrin clot properties are involved in thromboembolic events.•We identified about 500 proteins within healthy subjects plasma clots.•Fibrin clots are rich in proteins not related to coagulation and fibrinolysis.•Fibrin clot properties are associated with the protein content within plasma clots.