| First Author | McPherson HR | Year | 2021 |
| Journal | Elife | Volume | 10 |
| PubMed ID | 34633287 | Mgi Jnum | J:331248 |
| Mgi Id | MGI:6788571 | Doi | 10.7554/eLife.68761 |
| Citation | McPherson HR, et al. (2021) Fibrinogen alphaC-subregions critically contribute blood clot fibre growth, mechanical stability, and resistance to fibrinolysis. Elife 10:e68761 |
| abstractText | Fibrinogen is essential for blood coagulation. The C-terminus of the fibrinogen alpha-chain (alphaC-region) is composed of an alphaC-domain and alphaC-connector. Two recombinant fibrinogen variants (alpha390 and alpha220) were produced to investigate the role of subregions in modulating clot stability and resistance to lysis. The alpha390 variant, truncated before the alphaC-domain, produced clots with a denser structure and thinner fibres. In contrast, the alpha220 variant, truncated at the start of the alphaC-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 alphaC-subregions in fibrin polymerisation, clot mechanical strength, and fibrinolytic susceptibility. Furthermore, we demonstrate that the alphaC-subregions are key for promoting longitudinal fibre growth. Together, these findings highlight critical functions of the alphaC-subregions in relation to clot structure and stability, with future implications for development of novel therapeutics for thrombosis. |
