von Willebrand factor and occlusive arterial thrombosis. A study in normal and von Willebrand's disease pigs with diet-induced hypercholesterolemia and atherosclerosis

T C Nichols, D A Bellinger, D A Tate, R L Reddick, M S Read, G G Koch, K M Brinkhous, T R Griggs
1990 Arteriosclerosis An Official Journal of the American Heart Association Inc  
The thrombotic response of atherosclerotic arteries to stenosis and Injury was studied In 14 pigs, eight normal and six with von Willebrand's disease (vWD). Atherosclerosis was produced by feeding a 1% to 2% cholesterol diet for 24 weeks. Both groups of pigs developed severe hypercholesterolemia, greater than five times baseline values. Coronary atherosclerosis was detected in all vWD pigs and in all but one normal pig and was not significantly different between groups. At sacrifice under
more » ... crifice under general anesthesia, a Goldblatt clamp (GC) was positioned around the left anterior descending coronary (LAD) and carotid arteries to produce a stenotic segment, which was pinch-injured with needle holders. A 20 MHz Doppier velocity crystal was placed distal to the GC to detect cyclic flow reductions or permanent cessation of flow velocity indicative of occluslve thrombosis. In the phenotyplcally normal pigs with diet-Induced atherosclerosis, occlusive thrombosis was detected In seven of seven LAD and seven of seven carotid arteries. In atherosclerotic vWD pigs, occluslve thrombosis failed to form In six LAD and 10 carotid arteries (p<0.003, Wllcoxon rank sum test). Scanning electron micrographs demonstrated platelet-fibrin microthrombi in both groups of pigs; only phenotyplcally normal pigs had occluslve thrombi. Von Willebrand factor Is essential for the development of occluslve thrombosis and appears to support the progression of a mixed mlcrothrombus to an occlusive thrombus. (Arteriosclerosis 10:449-461,
doi:10.1161/01.atv.10.3.449 fatcat:cbgfk7djxfcmnby7iqxlsqrl2q