Platelet-collagen responses: molecular basis and therapeutic promise.
Exposure of circulating blood to collagen after vessel injury has been recognized as a primary event in arterial thrombosis for many years but an understanding of the molecular basis of this response has only recently materialized. Platelet collagen interactions are initiated indirectly by interaction of platelet glycoprotein Ib (GPIb) with collagen-bound von Willebrand Factor (vWF). Slowed, rolling platelets firmly adhere following the generation of platelet activating signals in a process initiated by the platelet collagen receptor glycoprotein VI (GPVI). The contribution of the first platelet collagen receptor identified, integrin alpha (2)beta (1), remains controversial. alpha (2)beta (1) is not required for platelet responses to collagen under many experimental conditions but GPVI and other intracellular signals may activate the integrin, which is likely to play a later, secondary role. In vivo studies of arterial thrombosis using genetically modified mice suggest that blockade of platelet-collagen interactions may be a highly effective means of inhibiting arterial thrombosis. Recent studies have generated a more complete model of the molecular basis of platelet-collagen responses and provided both the means and incentive to create novel therapeutic agents aimed at blocking this process to treat human atherothrombotic diseases such as myocardial infarction and stroke.
Kahn
Mark L
ML
Division of Cardiology and Department of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania 19104, USA. markkahn@mail.med.upenn.edu
D000818:Animals; D001792:Blood Platelets / Q000502:physiology*; D003094:Collagen / Q000502:physiology*; D006801:Humans; D051379:Mice; D010973:Platelet Adhesiveness; D019038:Platelet Glycoprotein GPIb-IX Complex / Q000502:physiology; D010980:Platelet Membrane Glycoproteins / Q000502:physiology; D015398:Signal Transduction; D014841:von Willebrand Factor / Q000502:physiology
D019038:Platelet Glycoprotein GPIb-IX Complex; D010980:Platelet Membrane Glycoproteins; C098341:platelet membrane glycoprotein VI; D014841:von Willebrand Factor; D003094:Collagen