title: Targeting shear stress-induced platelet activation: is lesion-specific antiplatelet therapy a realistic clinical goal?
abstract: Platelets are mediators of physiologic hemostasis and pathologic thrombosis. They operate within distinctive vascular and rheologic microenvironments, and their participation in hemostasis or thrombosis is directed by distinct variables operating within the microenvironment. Thrombosis is not simply too much hemostasis: there is good evidence that triggering mechanisms of platelet aggregation under low shear stress conditions are different from those operating under high shear stress conditions. Such differences are hypothesized to exist in vivo and to separate mechanisms of microvascular hemostasis from mechanisms of arterial thrombosis, such as those involved in myocardial, cerebral and peripheral vascular ischemia and infarction. This separation forms the conceptual basis for the hypothesis that lesion-specific antithrombotic agents might some day be invented that inhibit arterial thrombosis without causing bleeding that arises from impaired hemostasis. The focus of much of the work in this field has been platelet aggregation initiated by shear-dependent von Willebrand factor binding to the platelet glycoprotein Ib-IX-V complex. It is hypothesized that by elucidating molecular mechanisms of platelet activation operating under pathologically elevated shear stresses, targets of lesion-specific therapies will one day be identified for use in clinical syndromes of arterial thrombosis.
authors.affiliation: Michael E DeBakey VA Medical Center, Baylor College of Medicine, Houston, TX 77030, USA. mkroll@bcm.tmc.edu
authors.forename: Michael H
authors.initials: MH
authors.lastname: Kroll
authors.forename: Shuju
authors.initials: S
authors.lastname: Feng
mesh_terms: D000818:Animals; D006801:Humans; D015539:Platelet Activation / Q000187:drug effects* / Q000502:physiology*; D010975:Platelet Aggregation Inhibitors / Q000494:pharmacology*; D013314:Stress, Mechanical
chemical_list: D010975:Platelet Aggregation Inhibitors