Impaired fibrin gel permeability by high homocysteine levels

Abstract

Mechanisms involved in the relationship between hyperhomocysteinemia and thrombosis are still unclear. In previous reports we have shown that high homocysteine concentrations led to more compact and branched fibrin networks than controls. These clots showed an impaired lysis associated to their architecture. The aim of this study was to evaluate the effects of homocysteine on permeation of clots obtained from plasma and purified systems. Fibrin gels were prepared with normal plasma incubated with homocysteine and, in the purified systems, with fibrinogen and factor XIII treated with the amino acid. Permeability constants (K(s)) were determined through flow measurements. Linear regression curve between K(s) values and homocysteine levels in the plasmatic assays showed a negative correlation coefficient, r = -0.997 (p = 0.003). K(s) of fibrin gels obtained from purified systems with fibrinogen incubated with homocysteine was (7.07 ± 0.27) × 10(-9) cm(2), control was (11.40 ± 0.37) × 10(-9) cm(2) (n = 3; p < 0.01). K(s) of fibrin gels obtained with factor XIII treated with homocysteine was (1.47 ± 0.17) × 10(-9) cm (2), and control was (3.31 ± 0.31) × 10(-9) cm(2) (n = 3; p<0.01). Plasma incubated with high homocysteine concentrations produced fibrin clots significantly less permeable than controls in a dose dependent manner, and the results showed that fibrinogen and factor XIII were involved in that detrimental effect. These findings might explain the impaired fibrinolysis related to increased homocysteine levels and contribute to understanding the association between the amino acid and thrombosis.