Distinct antithrombotic consequences of platelet glycoprotein Ibalpha and VI deficiency in a mouse model of arterial thrombosis.
BACKGROUND
Collagen and von Willebrand factor (VWF) are considered essential to initiate platelet deposition at sites of vascular injury, but their respective roles remain to be elucidated.


METHODS
We used a model of carotid artery thrombosis induced by a ferric chloride injury to compare the time to first occlusion and occlusion rate at 25 min postinjury in mice lacking the collagen receptor, glycoprotein (GP) VI, or the ligand-binding domain of the VWF receptor, GP Ibalpha.


RESULTS
In normal mice used as controls (n = 12), a complete obstruction of blood flow developed within 8.05 +/- 0.47 min (mean +/- SEM), and the occlusion rate was 100%. The results were variable in 26 GP VI(-/-) mice. The artery never occluded in eight mice, but the time to first occlusion in the remaining 18 (8.36 +/- 0.27 min) was not different from normal (P = 0.556). Nonetheless, the occlusion rate was 42%, because in seven mice the occluded artery reopened and stayed patent at 25 min. In contrast, the artery never occluded in 12 mice lacking GP Ibalpha. In ex vivo perfusion experiments, GP VI(-/-) platelets failed to form thrombi onto collagen type I fibrils, but formed thrombi of normal size when exposed to endothelial or fibroblast extracellular matrix.


CONCLUSIONS
Absence of GP Ibalpha function has a more profound antithrombotic effect in vivo than absence of the GP VI-dependent pathway of collagen-induced adhesion/activation. Components of the extracellular matrix may elicit a thrombogenic response in the absence of GP VI but not GP Ibalpha.
Konstantinides
S
S
Department of Molecular and Experimental Medicine, Division of Experimental Hemostasis and Thrombosis, The Roon Center for Arteriosclerosis and Thrombosis, The Scripps Research Institute, La Jolla, CA, USA.
Ware
J
J
Marchese
P
P
Almus-Jacobs
F
F
Loskutoff
D J
DJ
Ruggeri
Z M
ZM
D000818:Animals; D001157:Arterial Occlusive Diseases / Q000517:prevention & control; D002341:Carotid Artery Thrombosis / Q000517:prevention & control*; D002712:Chlorides; D004195:Disease Models, Animal; D005290:Ferric Compounds; D051379:Mice; D018345:Mice, Knockout; D019038:Platelet Glycoprotein GPIb-IX Complex / Q000235:genetics*; D010980:Platelet Membrane Glycoproteins / Q000172:deficiency*
D002712:Chlorides; D005290:Ferric Compounds; D019038:Platelet Glycoprotein GPIb-IX Complex; D010980:Platelet Membrane Glycoproteins; C098341:platelet membrane glycoprotein VI; C024555:ferric chloride