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Effects of homocysteine on l ‐arginine transport and nitric oxide formation in human platelets
Author(s) -
Leoncini G.,
Pascale R.,
Signorello M. G.
Publication year - 2003
Publication title -
european journal of clinical investigation
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.164
H-Index - 107
eISSN - 1365-2362
pISSN - 0014-2972
DOI - 10.1046/j.1365-2362.2003.01203.x
Subject(s) - platelet , homocysteine , nitric oxide , arginine , chemistry , thrombin , platelet activation , medicine , endocrinology , biochemistry , amino acid , organic chemistry
Background Recent evidence indicates that hyperhomocysteinaemia is an independent risk factor for atherosclerosis, thrombosis and other cardiovascular diseases. This may be secondary to impaired fibrinolysis or increased platelet reactivity. Nitric oxide (NO), a product from l ‐arginine by NOS and potent antiaggregating agent, plays an important role in the regulation of platelet function. Design The present study aimed to define the effect of homocysteine on the l ‐arginine/NO pathway in human platelets. l ‐arginine uptake, NO formation and Ca 2+ levels were measured. Moreover the homocysteine effect on platelet activation induced by thrombin was tested. Results Homocysteine causes a concentration‐dependent inhibition of l ‐arginine transport. Results show that homocysteine does not modify the Km parameter, but it significantly decreases the Vmax value. The nitrite and nitrate formation, strictly correlated with the l ‐arginine transport, also significantly decreased. In contrast, cNOS activity remained unchanged upon homocysteine treatment. In addition homocysteine in a dose dependent manner increased the intracellular Ca 2+ concentration and platelet response to thrombin. Conclusions Results indicate that the l ‐arginine/NO pathway is one of the various targets of homocysteine in human platelets. The increased Ca 2+ levels associated with reduced NO formation may generate hyperactivation and may contribute to the thrombogenic processes.