EFFECTS OF HOMOCYSTEINE AND RELATED-COMPOUNDS ON PROSTACYCLIN PRODUCTION BY CULTURED HUMAN VASCULAR ENDOTHELIAL-CELLS

Elevated plasma homocysteine is associated with an increased risk of i ntravascular thrombosis. Platelet aggregation and thrombosis are inhib ited by prostacyclin produced by the vascular endothelium. Our aim was to investigate whether homocysteine and related metabolites inhibit e ndothelial prostacyclin production. We used a radioimmunoassay for 6-k etoprostaglandin-F-1 alpha to assay medium which had been in contact w ith confluent cultured endothelial cells. In medium containing 20% hum an serum, endothelial prostacyclin production was not specifically inh ibited by homocysteine, S-adenosylhomocysteine or protein-bound homocy steine. Further, there was no consistent difference in prostacyclin pr oduction by cells cultured in medium containing sera from homocystinur ia patients, compared with medium containing normal healthy sera. We c onclude that vascular disorder in homocystinuria is unlikely to result from effects of homocysteine or related metabolites on endothelial pr ostacyclin production. By contrast, S-adenosylhomocysteine and protein -bound homocysteine specifically inhibited prostacyclin production by cells cultured in medium containing 20% fetal calf serum.