Homocysteine modifies fibrin clot deformability: Another possible explanation of harm

摘要

Several studies have associated elevated plasma homocysteine (Hcy) levels with higher risk of thrombosis. In order to evaluate possible changes in fibrin strength and deformability mediated by Hcy, the effect of the amino acid on plasma fibrin clot was studied, measuring the viscoelastic clots response as a function of Hcy concentration added to plasma (final concentrations: 0, 50, 100, 250 and 500 μM). Storage (G') and loss (G") moduli were significantly higher than control at all Hcy concentrations evaluated in a dose-independent way (G'_(50μM Hcy) = 254 ± 10 Pa vs. 178 ± 30 Pa, p = 0.012; G"_(50μM Hcy) = 32 ± 1 Pa vs. 24 ± 2 Pa, p = 0.012). The tangent of the phase shift angles tan δ obtained from Hcy-clots with respect to control system proved to be unchanged (tan δ_(50μM Hcy) = 0.130 ± 0.007 Pa vs. 0.150 ± 0.020 Pa, NS). Increases observed in G' and G" values allowed us to conclude that Hcy action led to the stiffening of the clots formed in a dose independent way. The higher crosslinking of the fibrin network (higher G') contributed both to this structural behavior and to a higher compartmentalization and viscosity of the fluid phase (higher G") of the gel. The lower deformability of the clots formed after Hcy addition was also detected through deformation sweep assays. These material's characteristics may lead to pathological behavior, increasing the chances of obstruction in the blood vessels.