VON-WILLEBRAND-FACTOR DOES NOT INFLUENCE ATHEROGENESIS IN ARTERIES SUBJECTED TO ALTERED SHEAR-STRESS

The role of von Willebrand factor (vWF) in arterial neointimal formati on that develops in arteries with altered shear stress was investigate d using normal, heterozygous, and homozygous von Willebrand disease pi gs (ie, vWD, or lacking vWF) that were fed normal pig chow. Shear stre ss was applied to carotid and femoral arteries with a Goldblatt clamp for 14 days, producing a greater than or equal to 80% stenosis. Neoint imal lesion size was measured by computer-assisted morphometry, Expres sion of proliferative cell nuclear antigen (PCNA) by neointimal and me dial cells was used as a relative index of proliferative activity. For shear-stressed arteries, there was no significant difference in the n umber-of smooth muscle cell layers in the lesion, lesion size, and per cent of PCNA-positive neointimal or medial cells among normal, heteroz ygous, and homozygous vWD pigs (P greater than or equal to.1, ANOVA). Lesions in pigs that expressed VWF (normals and heterozygotes) contain ed large amounts of VWF in the neointima, whereas lesions in vWD pigs had no detectable VWF. Moreover, no foam cells were detected in the le sions, Thus, the absence of vWF apparently does not alter the size of lesions in shear-stressed arteries in vWD pigs or the number of neoint imal or medial cells expressing PCNA. Mechanism(s) involved with shear -induced modulation of smooth muscle cell proliferation, then, can ope rate independently of vWF in normolipemic pigs.