Homocysteine-induced inhibition of nitric oxide production in platelets: astudy on healthy and diabetic subjects

Aims/hypothesis. The molecular mechanisms involved in the platelet activati on observed in hyperhomocysteinemia are not known. We aimed to discover if homocysteine concentrations are associated with abnormal platelet nitric ox ide production in healthy and diabetic subjects. Methods. The study cohort included 28 patients with Type I (insulin-depende nt) diabetes mellitus, 30 patients with Type II (non-insulin-dependent) dia betes mellitus, and 34 healthy subjects. Homocysteine plasma concentrations were measured by high-performance liquid chromatography. Platelet nitric o xide production was measured using a nitric oxide meter before and after a 3-h incubation with 100 mu mol/l homocysteine. Stimulation experiments were done in vitro by the addition of alpha -thrombin (0.2 U/ml). Results. Basal platelet nitric oxide production was lower in diabetic patie nts than in healthy subjects. Nitric oxide release was reduced by in vitro homocysteine incubation. being lower in platelets from diabetic patients th an in platelets from control subjects. Thrombin increased nitric oxide synt hesis in platelets from healthy subjects both in the presence and absence o f homocysteine. In diabetic subjects thrombin increased nitric oxide releas e in the absence of homocysteine. But in the presence of homocysteine the r esponse was reduced. An inverse relation was found between plasma homocyste ine levels and basal platelet nitric oxide release in diabetic and healthy subjects. Conclusion/interpretation. Homocysteine could exert its atherogenic action in healthy and diabetic subjects partly by inhibiting platelet nitric oxide production with the subsequent increased platelet activation and aggregati on.