Aortic atherosclerosis in pigs with heterozygous von Willebrand disease. Comparison with homozygous von Willebrand and normal pigs.

Abstract

We have reported that pigs with severe homozygous von Willebrand disease (vWd) are resistant to spontaneous and high fat, high cholesterol, diet-induced atherosclerosis. In this study we report the quantitation of aortic atherosclerotic plaques in three groups of pigs fed with a high fat, high cholesterol (2%) diet from age 3 to 9 months. Nine normal pigs (normal factor VIII antigen, VIII R:AG, and ristocetin co-factor, VIII:RWF) had a mean of 21% atherosclerotic involvement of the distal aortic surface and a 4.5% mean involvement of the entire aorta. Five homozygous vWd pigs (undetected VIII R:AG and VIII:RWF) had a mean of 4.2% atherosclerotic involvement of the distal aortic surface and 1.2% involvement of the entire aorta (p less than 0.01, rank sum test). Five heterozygous vWd pigs (approximately 35% VIII R:AG and VIII:RWF) had a mean of 25% atherosclerotic involvement of the distal aortic surface and 6% involvement of the entire aorta; the results were not significantly different from those in the normal pigs. We concluded that resistance to atherosclerosis is not found in animals with moderate reduction of VIII R:AG and VIII:RWF. This may have implications for humans, since in human vWd both factors are almost always present.