Acid Sphingomyelinase Regulates Platelet Cell Membrane Scrambling, Secretion, and Thrombus Formation

Objective—Platelet activation is essential for primary hemostasis and acute thrombotic vascular occlusions. On activation, platelets release their prothrombotic granules and expose phosphatidylserine, thus fostering thrombin generation and thrombus formation. In other cell types, both degranulation and phosphatidylserine exposure are modified by sphingomyelinase-dependent formation of ceramide. The present study thus explored whether acid sphingomyelinase participates in the regulation of platelet secretion, phosphatidylserine exposure, and thrombus formation. Approach and Results—Collagen-related peptide–induced or thrombin-induced ATP release and P-selectin exposure were significantly blunted in platelets from Asm-deficient mice (Smpd1−/−) when compared with platelets from wild-type mice (Smpd1+/+). Moreover, phosphatidylserine exposure and thrombin generation were significantly less pronounced in Smpd1−/− platelets than in Smpd1+/+ platelets. In contrast, platelet integrin αIIbβ3 activation and aggrega...