GPVI deficiency in FcRgamma-null mice delayed initial thrombus formation and vessel occlusion after severe FeCl3 injury compared with wild-type mice, but laser-induced thrombus was comparable.
Does the absence of glycoprotein VI (GPVI) or the type of vascular injury affect arteriolar thrombus formation in mice?
The mechanism of thrombus formation depends heavily on the injury model, with GPVI-collagen interaction being crucial in FeCl3 injury but thrombin activation dominating in laser injury.
The role of the collagen receptor glycoprotein VI (GPVI) in arteriolar thrombus formation was studied in FcRgamma-null mice (FcRgamma(-/-)) lacking platelet surface GPVI. Thrombi were induced with severe or mild FeCl(3) injury. Collagen exposure was significantly delayed and diminished in mild compared with severe FeCl(3) injury. Times to initial thrombus formation and vessel occlusion were delayed in FcRgamma(-/-) compared with wild-type mice after severe injury. Platelet accumulation in wild-type mice was decreased after mild compared with severe injury. However, there was little difference between platelet accumulation after severe or mild injury in FcRgamma(-/-). These data indicate a significant role for GPVI in FeCl(3)-induced thrombus formation. Pretreatment of wild-type mice with lepirudin further impaired mild FeCl(3)-induced thrombus formation, demonstrating a role for thrombin. Laser-induced thrombus formation in wild-type and FcRgamma(-/-) was comparable. Collagen exposure to circulating blood was undetectable after laser injury. Normalized for thrombus size, thrombus-associated tissue factor was 5-fold higher in laser-induced thrombi than in severe FeCl(3)-induced thrombi. Thus, platelet activation by thrombin appears to be more important after laser injury than platelet activation by GPVI-collagen. It may thus be important when considering targets for antithrombotic therapy to use multiple animal models with diverse pathways to thrombus formation.
Dubois et al. (Fri,) conducted a other in Arteriolar thrombus formation. FcRgamma-null (GPVI deficiency) vs. Wild-type mice was evaluated on Times to initial thrombus formation and vessel occlusion. GPVI deficiency in FcRgamma-null mice delayed initial thrombus formation and vessel occlusion after severe FeCl3 injury compared with wild-type mice, but laser-induced thrombus was comparable.