Abstract
An elevated concentration of fibrinogen in blood is a significant risk factor during many pathological diseases, as it leads to an increase in red blood cells (RBC) aggregation, resulting in hemorheological disorders. Despite the biomedical importance, the mechanisms of fibrinogen-induced RBC aggregation are still debatable. One of the discussed models is the non-specific adsorption of fibrinogen macromolecules onto the RBC membrane, leading to the cells bridging in aggregates. However, recent works point to the specific character of the interaction between fibrinogen and the RBC membrane. Fibrinogen is the major physiological ligand of glycoproteins receptors IIbIIIa (GPIIbIIIa or αIIββ3 or CD41/CD61). Inhibitors of GPIIbIIIa are widely used in clinics for the treatment of various cardiovascular diseases as antiplatelets agents preventing the platelets’ aggregation. However, the effects of GPIIbIIIa inhibition on RBC aggregation are not sufficiently well studied. The objective of the present work was the complex multimodal in vitro study of the interaction between fibrinogen and the RBC membrane, revealing the role of GPIIbIIIa in the specificity of binding of fibrinogen by the RBC membrane and its involvement in the cells’ aggregation process. We demonstrate that GPIIbIIIa inhibition leads to a significant decrease in the adsorption of fibrinogen macromolecules onto the membrane, resulting in the reduction of RBC aggregation. We show that the mechanisms underlying these effects are governed by a decrease in the bridging components of RBC aggregation forces.
Highlights
The multicomponent blood system is responsible for the stability of hemodynamic processes and high effectiveness of microcirculation [1,2,3]
To provide the non-specific binding control test, we studied the effects of GPIIbIIIa inhibitors on the sorption of fluorescein isothiocyanate (FITC)-labeled human serum albumin (HSA)
We visualized the adsorption of fibrinogen macromolecules onto the red blood cells (RBC) membrane with the usage of optical tweezers combined with a microfluidics setup
Summary
The multicomponent blood system is responsible for the stability of hemodynamic processes and high effectiveness of microcirculation [1,2,3]. The reversible aggregation of red blood cells (RBC) is crucial for regulating the blood viscosity changes at low shear stress and hydrodynamic resistance in blood circulation [4,5,6], while coagulation (clotting) serves as a governing mechanism of bleeding prevention [7]. Both of these processes involve fibrinogen, a blood plasma protein, which is a dimeric molecule composed of pairs of α, β, and γ chains that are folded into a three-domain nodular structure [8,9]. A complex study of the interaction between fibrinogen molecules and RBC will allow developing new approaches of the targeted treatment of hemorheological disfunctions caused by an evaluated fibrinogen-induced aggregation of RBC
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