A critical role of platelet glycoprotein Ibα in arterial remodeling.

T he canonical role of platelets is hemostasis in which they function as highly specialized cells designed to plug holes in the blood vascular system. To accomplish this task, platelets have evolved unique molecular tools that enable them to function in the vascular environment, such as the GPIbα receptor complex that mediates platelet adhesion to the vessel wall in the face of high shear forces and stringent activation pathways that trigger adhesive interactions mediated by integrin receptors. It is becoming increasing apparent that platelets may also use these specialized molecular tools to perform vascu-lar tasks other than plugging holes and preventing blood loss. Some of these more recently defined roles seem to be variants of their canonical role, for example, lymphovenous hemosta-sis that controls the flow of lymph into the blood circulation, 1 and inflammatory hemostasis that prevents bleeding at sites of extremely high vascular permeability. 2 Others seem to be truly nonhemostatic, for example, platelet adhesion to leukocytes to facilitate their passage across blood vessel wall at sites of inflammation. 3,4 Common to these noncanonical platelet roles is the use of unique molecular mechanisms that allow platelets to respond to stimuli in the vascular environment that may be physical (eg, shear), cellular (eg, blood versus lymphatic endothelium), or molecular (eg, platelet activators such as thrombin, ADP). In the present issue of ATVB, Chandraratne et al 5 describe a new role for platelets and for GPIbα, the platelet-specific receptor that enables cellular adhesion under shear, 6 during the formation of collateral arteries after femoral arterial liga-tion (a process termed arteriogenesis, although it involves expansion of existing vessels rather than the growth of new ones). Using in vivo microscopy, they observe transient adhesion of platelets to the endothelium of small arteries destined to become collateral vessels shortly after femoral artery liga-tion and to that of adjacent veins as well. Platelet adhesion is dependent on the function of GPIbα, a receptor that binds endothelial-derived von Willebrand's factor under high shear forces, and is coincident with firm leukocyte adhesion to the walls of those vessels. Loss of platelet GPIbα reduces leukocyte adhesion and migration across the walls of developing collateral vessels. The formation of platelet-leukocyte complexes is observed in whole blood shortly after femoral artery ligation, and loss of either platelets or GPIbα receptor function impairs the recovery of blood flow that results from collateral vessel expansion. These studies identify a role for …