Localized reduction of atherosclerosis in von Willebrand factor-deficient mice

Blood. 2001 Sep 1;98(5):1424-8. doi: 10.1182/blood.v98.5.1424.

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.

Publication types

  • Comparative Study
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Antigens, CD / metabolism
  • Aorta / pathology
  • Aortic Diseases / complications
  • Aortic Diseases / genetics
  • Aortic Diseases / pathology
  • Arteriosclerosis / blood*
  • Arteriosclerosis / complications
  • Arteriosclerosis / genetics
  • Arteriosclerosis / pathology
  • Cell Adhesion
  • Chemotaxis, Leukocyte
  • Crosses, Genetic
  • Diet, Atherogenic
  • Female
  • Genetic Predisposition to Disease
  • Integrin beta3
  • Leukocytes / pathology
  • Ligands
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Platelet Membrane Glycoproteins / metabolism
  • Receptors, LDL / deficiency
  • Receptors, LDL / genetics
  • Sinus of Valsalva / pathology
  • von Willebrand Diseases / complications*
  • von Willebrand Diseases / genetics
  • von Willebrand Diseases / pathology
  • von Willebrand Factor / genetics
  • von Willebrand Factor / physiology*

Substances

  • Antigens, CD
  • Integrin beta3
  • Ligands
  • Platelet Membrane Glycoproteins
  • Receptors, LDL
  • von Willebrand Factor