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Blood, 1 September 2001, Vol. 98, No. 5, pp. 1424-1428
HEMOSTASIS, THROMBOSIS, AND VASCULAR BIOLOGY
Localized reduction of atherosclerosis in von Willebrand
factor-deficient mice
Nassia Methia,
Patrick André,
Cécile V. Denis,
Maria Economopoulos, and
Denisa D. Wagner
From the Center for Blood Research and the Department
of Pathology, Harvard Medical School, Boston, MA.
To examine the role of the platelet adhesion molecule von
Willebrand factor (vWf) in atherogenesis, vWf-deficient mice
(vWf / ) were bred with mice lacking the low-density
lipoprotein receptor (LDLR / ) on a C57BL/6J background.
LDLR / vWf+/+ and LDLR / vWf / mice were placed on a diet rich
in saturated fat and cholesterol for different lengths of time. The
atherogenic diet stimulated leukocyte rolling in the mesenteric venules
in both genotypes, indicating an increase in P-selectin-mediated
adhesion to the endothelium. After 8 weeks on the atherogenic diet, the
fatty streaks formed in the aortic sinus of LDLR / vWf / mice of
either sex were 40% smaller and contained fewer monocytes than those in LDLR / vWf+/+ mice. After 22 weeks on the atherogenic diet (early
fibrous plaque stage), the difference in lesion size in the aortic
sinus persisted. Interestingly, the lesion distribution in the aortas
of LDLR / vWf / animals was different from that of
LDLR / vWf+/+ animals. In vWf-positive mice, half of all
lesions were located at the branch points of the renal and mesenteric arteries, whereas lesions in this area were not as prominent in the
vWf-negative mice. These results indicate that the absence of vWf
primarily affects the regions of the aorta with disturbed flow that are
prone to atherosclerosis. Thus, vWf may recruit platelets/leukocytes to
the lesion in a flow-dependent manner or may be part of the
mechano-transduction pathway regulating endothelial response to shear stress.

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