Fibrinogen and fibrin play an important role in blood clotting, fibrinolysis, inflammation, wound healing, angiogenesis, cellular and matrix interactions. The contribution of fibrin(ogen) to these processes largely depends on the characteristics of the fibrin(ogen) itself, but also on specific interactions with proenzymes, clotting factors, enzyme inhibitors, and cell receptors. This moment fibrin deposits functions relating to matrix formation for adhesion and migration of endothelial and stem cells, fibroblasts, ets; proliferative, secretory and migration cell activity regulation, accumulation of growth factors in regeneration zone, localization of inflammation area, and regulation of blood vessels state are facts. Fibrin is a unique material and is used as a sealant or glue, a matrix for cells, a scaffold for tissue engineering, and a carrier or a vector for targeted drug delivery. The wound healing depends significantly on the fibrin clot structure. The fibrin clot structure is not stiff due to many factors. Clot properties in turn are largely governed by the fiber diameters, branching, pore sizes and the degree of factor XIIIa-mediated fibrin cross-linking. Variability of fibrinogen molecule can play significant role at the clot structure shift and is determined by genetic as a substitute folding. It has been shown in vitro that clots formed at different fibrinogen concentration have variable structure. At low concentrations of fibrinogen relative to the level of active thrombin, the clot is composed of thick fibrils, since a low probability of equilateral association increases at low concentrations of fibrin-monomer and protofibrils. In contrast, at high concentrations, the diameter of the fibrils is much thinner, which is likely due to the accelerated formation of fibrin-monomer. It is known, that both the concentration of fibrinogen and activation level of prothrombin are quite labile under iv vivo.
firstly, by the indirect translocation of the fibrin around the lipid membrane, where it binds with αIIbβ3 and interacts with the platelets, and secondly – by the maintenance of red blood cells in the clot. This mechanism is able to modulate the size of the thrombus through the cross-linking of the fibrin Aα-chains. The fact that such molecular transitions occur at the small deformations created by cells and manifest themselves directly in the macroscopic mechanics of fibrin can be an example of the forced unfolding of the protein structure. Unfolded domains can be a purpose of tissue engineering and molecular biology that means creating more rigid fibrin sealants that are used for surgical intervention. The control of unfolding can also lead to the development of new strategies for the breaking thrombi, possibly by stabilizing the coiled-coil, which makes the clots more fragile, or by destabilizing the coiled-coil, making clots milder and less occlusive. Thus, the variability of the fibrin clots structure is predicted by the very structure of the fibrinogen molecule and the nature of its interaction with the factor XIII and other blood plasma proteins. This variability makes it possible to fine-tune the exposure of those adhesion sites, the availability of plasmin hydrolysis and proteolysis by other enzymes, etc. These are features that explain a differences in fibrin lifetimes and the amount of fibrin deposits for different types of inflammation. The proposed review examines the main factors that influence the structure of the clot and their effect on the performance of fibrin deposits of their functions.
Full text: PDF (Ukr) 1.65M