von Willebrand factor does not influence atherogenesis in arteries subjected to altered shear stress.
The role of von Willebrand factor (vWF) in arterial neointimal formation that develops in arteries with altered shear stress was investigated using normal, heterozygous, and homozygous von Willebrand disease pigs (ie, vWD, or lacking vWF) that were fed normal pig chow. Shear stress was applied to carotid and femoral arteries with a Goldblatt clamp for 14 days, producing a > or = 80% stenosis. Neointimal lesion size was measured by computer-assisted morphometry. Expression of proliferative cell nuclear antigen (PCNA) by neointimial and medial cells was used as a relative index of proliferative activity. For shear-stressed arteries, there was no significant difference in the number of smooth muscle cell layers in the lesion, lesion size, and percent of PCNA-positive neointimal or medial cells among normal, heterozygous, and homozygous vWD pigs (P> or =.1, ANOVA). Lesions in pigs that expressed vWF (normals and heterozygotes) contained large amounts of vWF in the neointima, whereas lesions in vWD pigs had no detectable vWF. Moreover, no foam cells were detected in the lesions. Thus, the absence of vWF apparently does not alter the size of lesions in shear-stressed arteries in vWD pigs or the number of neointimal or medial cells expressing PCNA. Mechanism(s) involved with shear-induced modulation of smooth muscle cell proliferation, then, can operate independently of vWF in normolipemic pigs.
Nichols
T C
TC
Department of Medicine, The Center for Thrombosis and Hemostasis, University of North Carolina at Chapel Hill, 27514-7075, USA. tnichols@med.unc.edu
Bellinger
D A
DA
Reddick
R L
RL
Koch
G G
GG
Sigman
J L
JL
Erickson
G
G
du Laney
T
T
Johnson
T
T
Read
M S
MS
Griggs
T R
TR
D000818:Animals; D001161:Arteriosclerosis / Q000209:etiology*; D001783:Blood Flow Velocity / Q000502:physiology; D002339:Carotid Arteries / Q000473:pathology / Q000503:physiopathology*; D005260:Female; D005263:Femoral Artery / Q000473:pathology / Q000503:physiopathology*; D006579:Heterozygote; D006720:Homozygote; D006801:Humans; D008297:Male; D013314:Stress, Mechanical; D013552:Swine; D017539:Tunica Intima / Q000503:physiopathology; D014842:von Willebrand Diseases / Q000473:pathology / Q000503:physiopathology; D014841:von Willebrand Factor / Q000235:genetics / Q000378:metabolism / Q000502:physiology*
D014841:von Willebrand Factor