☆ 4.5 Article

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

JOURNAL OF PROTEOMICS (2019)

Journal

JOURNAL OF PROTEOMICS

Volume 208, Issue -, Pages -

Publisher

ELSEVIER

DOI: 10.1016/j.jprot.2019.103487

Keywords

Fibrin; Clot; Proteomics; Clot properties

Funding

Max-Planck Society for the Advancement of Science
German Research Foundation (DFG/Gottfried Wilhelm Leibniz Prize)
Jagiellonian University Medical College [K/ZDS/007717]

Ask authors/readers for more resources

Protocol

Community support

Reagent

Community support

Abstract

Background: 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. Methods: We studied 20 healthy subjects aged 31-49 years in whom plasma fibrin clot permeability (K-s) and clot lysis time (CLT) were determined. A proteomic analysis of plasma fibrin clots was based on quantitative liquid chromatography-mass spectrometry. Results: 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%). alpha(2)-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-alpha and -gamma chains were associated with age, while body-mass index with clot-bound apolipoproteins (all p <.05). K-s correlated with fibrinogen-gamma and PF4 amounts within plasma clots. CLT was associated with fibrinogen-alpha and -gamma, PF4, and HRG (all p <.05). Conclusions: 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-gamma chain, platelet-derived PF4, and HRG. Significance: Our study for the first time suggests that more permeable fibrin clots with enhanced lysability contain less fibrinogen-gamma 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.

Authors

I am an author on this paper

Click your name to claim this paper and add it to your profile.

Reviews

Primary Rating

4.5

Not enough ratings

Secondary Ratings

Novelty

Significance

Scientific rigor

Rate this paper

Fibrin clot properties in cardiovascular disease: from basic mechanisms to clinical practice

Michal Zabczyk, Robert A. S. Ariens, Anetta Undas

Summary: Fibrinogen conversion and clot formation are crucial processes in coagulation cascade. Dense fibrin networks that are resistant to lysis have been associated with cardiovascular disease, while hypofibrinolysis is a persistent feature in patients with thrombotic events or stable coronary artery disease. Lifestyle modifications and certain medications can improve fibrin structure and function. Prospective studies have shown that prothrombotic fibrin clot phenotype can predict cardiovascular events. Furthermore, various factors, including mutations in fibrinogen molecules and clot-bound proteins, contribute to the prothrombotic fibrin clot phenotype. This review summarizes the mechanisms underlying unfavorable fibrin clot properties and their implications in cardiovascular disease and its thrombo-embolic manifestations.

CARDIOVASCULAR RESEARCH (2023)