Role of von Willebrand factor in arterial thrombosis. Studies in normal and von Willebrand disease pigs.
With normal and von Willebrand disease (vWD) pigs, we studied the role of von Willebrand factor (vWF) in platelet-vessel wall interactions and occlusive arterial thrombosis. Two methods of arterial injury have been used to determine the thrombotic response of flowing blood in vivo. The first involves balloon catheter injury. After superficial denudation of endothelium from coronary intima, platelets adhere to the subendothelium in a monolayer. Similar numbers of adherent platelets are found in both phenotypes, but platelets in vWD pigs have impaired pseudopod formation and are less well spread morphological indexes of limited platelet activation. Deeper injury, which involves the media, produces nonocclusive platelet-fibrin microthrombi. The second injury method involves pinching the artery at a site of superimposed stenosis, a procedure that almost always exposes media. This procedure induces platelet-fibrin microthrombi in normal and vWD pigs, but only normal pigs develop occlusive thrombosis. Both methods of arterial injury have also been performed in normal and vWD pigs with diet-induced hypercholesterolemia and atherosclerosis. Atherosclerosis promotes platelet spread in vWD pigs but does not abolish the protection from stenosis and injury-induced occlusive thrombosis. In addition, neutralization of vWF activity in normal pigs by a monoclonal antibody prevents the induction of occlusive thrombosis by the stenosis and pinch-injury procedure. This monoclonal antibody also causes performed platelet aggregates to break up. These experimental models of inducing arterial thrombosis have been used in normal and vWD pigs to demonstrate interactions between normal and atherosclerotic vessel wall constituents, circulating platelets and vWF that are fundamental in the process of arterial thrombosis.
Nichols
T C
TC
Department of Medicine, School of Medicine, University of North Carolina, Chapel Hill.
Bellinger
D A
DA
Reddick
R L
RL
Read
M S
MS
Koch
G G
GG
Brinkhous
K M
KM
Griggs
T R
TR
D000818:Animals; D001157:Arterial Occlusive Diseases / Q000503:physiopathology*; D001161:Arteriosclerosis / Q000503:physiopathology; D006937:Hypercholesterolemia / Q000503:physiopathology; D012016:Reference Values; D013552:Swine; D013927:Thrombosis / Q000503:physiopathology*; D014842:von Willebrand Diseases / Q000503:physiopathology*; D014841:von Willebrand Factor / Q000502:physiology*
D014841:von Willebrand Factor