Evidence that fibrinogen γ′ regulates plasma clot structure and lysis and relationship to cardiovascular risk factors in black Africans

Abstract

AbstractFibrinogen γ′ is known to influence fibrin clot structure in purified experimental models, but little is known regarding its influence on clot structure in plasma. Furthermore, the environmental and biological factors that affect its concentration are poorly described. We analyzed fibrinogen γ′, total fibrinogen concentration, and fibrin clot structure in 2010 apparently healthy black South Africans and related them to traditional cardiovascular disease (CVD) risk factors. Fibrinogen γ′ generally increased with increasing fibrinogen concentration, but a decreased γ′/total fibrinogen ratio was found at the highest total fibrinogen concentrations. Clot maximum absorbance increased with total fibrinogen and fibrinogen γ′, but decreased with γ'/total fibrinogen ratio. Clot lysis time showed a stronger relationship with fibrinogen γ′ than with total fibrinogen, whereby increased fibrinogen γ′ delayed clot lysis. CVD risk factors (excluding fibrinogen) explained 20% and 3%, respectively, of the variance in fibrinogen γ′ and the γ′/total fibrinogen ratio, with C-reactive protein making the biggest contribution. More than 50% of the variance in fibrinogen γ′ and γ′/total fibrinogen ratio is explained by factors other than total fibrinogen or other traditional CVD risk factors. Our data show that fibrinogen γ′ modulates plasma clot structure and fibrinolysis and is also influenced by factors other than fibrinogen.