Homocysteine thiolactone, N-homocysteine thiolactonyl retinamide, and platelet aggregation.

Because of platelet abnormalities, thrombosis and arteriosclerosis observed in human and experimental homocysteinemia, the effects of several chemical forms of homocysteine were studied in human platelets in vitro. The free base of homocysteine thiolactone caused primary platelet aggregation over a wide range of concentration (4 X 10(-8) to 10 micrograms/ml), but polar salts of homocysteine thiolactone, homocystine, homocysteine, and homocysteic acid were inactive. N-homocysteine thiolactonyl retinamide and trans retinoic acid caused aggregation at 100 micrograms/ml. Homocysteine thiolactone caused thromboxane TXB2 and prostacyclin 6-keto-PGF1 alpha formation during aggregation, but there was no release of ATP. This finding demonstrates dissociation between aggregation and release of dense granule content. Accumulation of the free base of homocysteine thiolactone may explain abnormal platelet function and thrombosis in human and experimental homocysteinemia.