Journal article
Two distinct pathways regulate platelet phosphatidylserine exposure and procoagulant function
SM Schoenwaelder, Y Yuan, EC Josefsson, MJ White, Y Yao, KD Mason, LA O'Reilly, KJ Henley, A Ono, S Hsiao, A Willcox, AW Roberts, DCS Huang, HH Salem, BT Kile, SP Jackson
Blood | AMER SOC HEMATOLOGY | Published : 2009
Abstract
Procoagulant platelets exhibit hallmark features of apoptotic cells, including membrane blebbing, microvesiculation, and phosphatidylserine (PS) exposure. Although platelets possess many well-known apoptotic regulators, their role in regulating the procoagulant function of platelets is unclear. To clarify this, we investigated the consequence of removing the essential mediators of apoptosis, Bak and Bax, or directly inducing apoptosis with the BH3 mimetic compound ABT-737. Treatment of platelets with ABT-737 triggered PS exposure and a marked increase in thrombin generation in vitro. This increase in procoagulant function was Bak/Bax- and caspase-dependent, but it was unaffected by inhibitor..
View full abstractGrants
Awarded by National Heart Foundation of Australia (Melbourne, Australia)
Awarded by National Health and Medical Research Council of Australia (Canberra, Australia)
Awarded by IRIISS
Awarded by Leukemia & Lymphoma Society (White Plains, NY)
Funding Acknowledgements
This work was supported by the National Heart Foundation of Australia (Melbourne, Australia; project grant G 06M 2617 to S.M.S.), the National Health and Medical Research Council of Australia (Canberra, Australia; project grant 516725; program grants 461221, 461219, IRIISS 361646; and fellowships to S.P.J., B.T.K., L.A.O., A.W.R., and D.C.S.H.), the Australian Research Council (Canberra, Australia; QEII fellowship to B.T.K.), the Victorian Cancer Agency (Carlton, Australia; fellowship to K.D.M.), a Victorian State Government OIS grant, the Cancer Council of Victoria (Carlton, Australia), the Sylvia and Charles Viertel Charitable Foundation (Melbourne, Australia; fellowship to B.T.K.), the Swedish Research Council (Stockholm, Sweden; fellowship to E.C.J.), and the Leukemia & Lymphoma Society (White Plains, NY; fellowship to E.C.J.; SCOR 7015-02).