HYPERHOMOCYSTEINEMIA MODULATES VEGF PLASMA LEVELS AND ITS EXPRESSION IN LEUCOCYTES IN HEALTHY SUBJECTS AND IN PATIENTS WITH PERIPHERAL ARTERIAL DISEASE AND DIABETES MELLITUS

Aim: Both homocysteine and vascular endothelial growth factor (VEGF) are implicated in development and progression of atherothrombotic vascular disease. We sought to determine whether there is a relationship between homocysteine and VEGF in healthy individuals and in patients with peripheral arterial disease (PAD) or diabetes mellitus (DM).Methods: Measurements of plasma homocysteine and VEGF and expression of VEGF in leucocytes were performed before and after intervention. Twelve healthy individuals were evaluated before and 4 h after methionine loading, whereas 10 patients with PAD and 15 patients with DM were evaluated before and 6 weeks after oral administration ofB vitamins and folate.Results: Basal homocysteine was elevated in patients with PAD and DM (21.5±.9 and 19.9±1 iimol/l, respectively). Methionine resulted in significant elevation, while B vitamins resulted in significant reduction of homocysteine and VEGF and there was a significant correlation between homocysteine and VEGF changes (r = 0.73, p 0.01). Moreover, VEGF mRNA expression in leucocytes was upregulated after methionine loading and was downregulated after B vitamins and folate treatment.Conclusion: These findings demonstrate that B vitamins and folate can successfully lower plasma homocysteine and VEGF expression in leucocytes in patients with PAD and DM