McPherson, H.R., Duval, C. orcid.org/0000-0002-4870-6542, Baker, S.R. et al. (10 more authors) (2021) Fibrinogen αC-subregions critically contribute blood clot fibre growth, mechanical stability and resistance to fibrinolysis. [Preprint]
Abstract
Fibrinogen is essential for blood coagulation. The C-terminus of the fibrinogen α-chain (αC-region) is composed of an αC-domain and αC-connector. Two recombinant fibrinogen variants (α390 and α220) were produced to investigate the role of subregions in modulating clot stability and resistance to lysis. The α390 variant, truncated before the αC-domain, produced clots with a denser structure and thinner fibres. In contrast, the α220 variant, truncated at the start of the αC-connector, produced clots that were porous with short stunted fibres and visible fibre ends. These clots were mechanically weak and susceptible to lysis. Our data demonstrate differential effects for the αC-subregions in fibrin polymerisation, clot mechanical strength, and fibrinolytic susceptibility. Furthermore, we demonstrate that the αC-subregions are key for promoting longitudinal fibre growth. Together, these findings highlight critical functions of the αC-subregions in relation to clot structure and stability, with future implications for development of novel therapeutics for thrombosis.
Metadata
Item Type: | Preprint |
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Authors/Creators: |
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Dates: |
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Institution: | The University of Leeds |
Academic Units: | The University of Leeds > Faculty of Medicine and Health (Leeds) > School of Medicine (Leeds) > Leeds Institute of Cardiovascular and Metabolic Medicine (LICAMM) > Discovery & Translational Science Dept (Leeds) |
Depositing User: | Symplectic Publications |
Date Deposited: | 13 Aug 2024 12:36 |
Last Modified: | 13 Aug 2024 12:36 |
Status: | Published |
Publisher: | bioRxiv |
Identification Number: | 10.1101/2021.05.07.443174 |
Open Archives Initiative ID (OAI ID): | oai:eprints.whiterose.ac.uk:215988 |