Homocysteine and its thiolactone-mediated modification of fibrinogen affect blood platelet adhesion.
Homocysteine (Hcys) and homocysteine thiolactone (HTL) concentrations in organism are correlated with a number of serious pathologies. In the literature, there are few papers describing studies on the effects of homocysteine on proteins that participate in blood coagulation and fibrinolysis in human. However, mechanisms involved in the relationship between hyperhomocysteinemia and hemostatic process are still unclear. The role of N- or S-homocysteinylation (induced by Hcys and its derivatives) of different hemostatic proteins, including fibrinogen is also still poorly known. The aim of this study was to establish the functional changes of the fibrinogen molecule induced by Hcys (at final doses of 10-100 µM) and the most reactive form of Hcys - its cyclic thioester, homocysteine thiolactone (0.1-1 µM), and to examine the effects of these changes on the capability of fibrinogen to interact with human blood platelets (by measuring the platelet adhesion). Our present results demonstrated that Hcys-treated fibrinogen in comparison with native molecule had a distinct capability to mediate platelet adhesion. Both, unstimulated and thrombin-activated platelets showed a reduced ability to adhere to Hcys-mediated fibrinogen. HTL (at all tested concentrations) had similar properties when we used thrombin-activated platelets. In conclusion, the results reported in this study could be useful for a better understanding of changes in hemostasis during hyperhomocysteinemia.
Joanna
J
Malinowska
Beata
B
Olas
D000328:Adult; D001792:Blood Platelets / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism*; D005340:Fibrinogen / Q000378:metabolism*; D006487:Hemostasis / Q000187:drug effects; D006710:Homocysteine / Q000031:analogs & derivatives* / Q000097:blood* / Q000494:pharmacology; D006801:Humans; D020138:Hyperhomocysteinemia / Q000097:blood; D010973:Platelet Adhesiveness / Q000187:drug effects; D055815:Young Adult
D006710:Homocysteine; D005340:Fibrinogen; C007957:homocysteine thiolactone