title: Pathologic high shear stress induces apoptosis events in human platelets.
abstract: Recently, it has been discovered that apoptosis of anucleate platelets can be induced by chemical agonists. Other studies demonstrated that mechanical forces (shear stresses) stimulate platelet activation and signaling in the absence of exogenous chemical stimuli. We analyzed whether shear stresses can trigger platelet apoptosis, a question that has not yet been studied. Using a cone-and-plate viscometer, we exposed human platelet-rich plasma to different shear stresses, ranging from physiologic arterial and arteriole levels (10-44 dyn/cm2) to pathologic high levels (117-388 dyn/cm2) occurring in stenotic vessels. We found that pathologic shear stresses induce not only platelet activation (P-selectin upregulation and GPIbalpha downregulation) but also trigger apoptosis events, including mitochondrial transmembrane potential depolarization, caspase 3 activation, phosphatidylserine exposure, and platelet shrinkage and fragmentation, whereas physiological shear stresses are not effective. This novel finding suggests that shear-induced platelet apoptosis can be mediated by mechanoreceptors, does not require nuclear participation, and may affect platelet clearance.
authors.affiliation: Division of Transfusion Medicine, Department of Laboratory Medicine and Pathobiology, St. Michael's Hospital, Toronto, Ont., Canada M5B 1W8. leytinv@smh.toronto.on.ca
authors.forename: Valery
authors.initials: V
authors.lastname: Leytin
authors.forename: David J
authors.initials: DJ
authors.lastname: Allen
authors.forename: Sergiy
authors.initials: S
authors.lastname: Mykhaylov
authors.forename: Lukasz
authors.initials: L
authors.lastname: Mis
authors.forename: Elena V
authors.initials: EV
authors.lastname: Lyubimov
authors.forename: Bernadette
authors.initials: B
authors.lastname: Garvey
authors.forename: John
authors.initials: J
authors.lastname: Freedman
mesh_terms: D017209:Apoptosis; D001792:Blood Platelets / Q000166:cytology* / Q000187:drug effects / Q000648:ultrastructure; D005434:Flow Cytometry; D006801:Humans; D008855:Microscopy, Electron, Scanning; D015539:Platelet Activation