DOI: 10.1182/blood.v98.5.1424. Localized reduction of atherosclerosis in von Willebrand factor

Localized reduction of atherosclerosis in von Willebrand factor–deficient mice

10.1182/blood.v98.5.1424

Crossref journal-article

American Society of Hematology

Blood (234)

Abstract

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.

Bibliography

Methia, N., AndreÌ, P., Denis, C. V., Economopoulos, M., & Wagner, D. D. (2001). Localized reduction of atherosclerosis in von Willebrand factorâdeficient mice. Blood, 98(5), 1424â1428.

Authors 5

Nassia Methia (first)
Patrick André (additional)
Cécile V. Denis (additional)
Maria Economopoulos (additional)
Denisa D. Wagner (additional)

References 41 Referenced 167

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Dates

Type	When
Created	23 years ago (July 27, 2002, 8:46 a.m.)
Deposited	4 years, 2 months ago (May 26, 2021, 5:26 a.m.)
Indexed	1 day, 8 hours ago (Aug. 24, 2025, 7:06 p.m.)
Issued	23 years, 11 months ago (Sept. 1, 2001)
Published	23 years, 11 months ago (Sept. 1, 2001)
Published Print	23 years, 11 months ago (Sept. 1, 2001)

Funders 0

None

BibTeX

@article{Methia_2001, title={Localized reduction of atherosclerosis in von Willebrand factor–deficient mice}, volume={98}, ISSN={0006-4971}, url={http://dx.doi.org/10.1182/blood.v98.5.1424}, DOI={10.1182/blood.v98.5.1424}, number={5}, journal={Blood}, publisher={American Society of Hematology}, author={Methia, Nassia and André, Patrick and Denis, Cécile V. and Economopoulos, Maria and Wagner, Denisa D.}, year={2001}, month=sep, pages={1424–1428} }

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  "abstract": "<jats:p>To examine the role of the platelet adhesion molecule von Willebrand factor (vWf) in atherogenesis, vWf-deficient mice (vWf\u2212/\u2212) were bred with mice lacking the low-density lipoprotein receptor (LDLR\u2212/\u2212) on a C57BL/6J background. LDLR\u2212/\u2212vWf+/+ and LDLR\u2212/\u2212vWf\u2212/\u2212 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\u2013mediated adhesion to the endothelium. After 8 weeks on the atherogenic diet, the fatty streaks formed in the aortic sinus of LDLR\u2212/\u2212vWf\u2212/\u2212 mice of either sex were 40% smaller and contained fewer monocytes than those in LDLR\u2212/\u2212vWf+/+ 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\u2212/\u2212vWf\u2212/\u2212 animals was different from that of LDLR\u2212/\u2212 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.</jats:p>",
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