Localized reduction of atherosclerosis in von Willebrand factor-deficient mice

被引:160
作者
Methia, N
André, P
Denis, CV
Economopoulos, M
Wagner, DD
机构
[1] Harvard Univ, Sch Med, Ctr Blood Res, Boston, MA 02115 USA
[2] Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA
关键词
D O I
10.1182/blood.V98.5.1424
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
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. (C) 2001 by The American Society of Hematology.
引用
收藏
页码:1424 / 1428
页数:5
相关论文
共 41 条
  • [31] Blocking very late antigen-4 integrin decreases leukocyte entry and fatty streak formation in mice fed an atherogenic diet
    Shih, PT
    Brennan, ML
    Vora, DK
    Territo, MC
    Strahl, D
    Elices, MJ
    Lusis, AJ
    Berliner, JA
    [J]. CIRCULATION RESEARCH, 1999, 84 (03) : 345 - 351
  • [32] Suppression of diet-induced atherosclerosis in low density lipoprotein receptor knockout mice overexpressing lipoprotein lipase
    Shimada, M
    Ishibashi, S
    Inaba, T
    Yagyu, H
    Harada, K
    Osuga, J
    Ohashi, K
    Yazaki, Y
    Yamada, N
    [J]. PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1996, 93 (14) : 7242 - 7246
  • [33] Shear-dependent changes in the three-dimensional structure of human von Willebrand factor
    Siedlecki, CA
    Lestini, BJ
    KottkeMarchant, K
    Eppell, SJ
    Wilson, DL
    Marchant, RE
    [J]. BLOOD, 1996, 88 (08) : 2939 - 2950
  • [34] TANGIRALA RK, 1995, J LIPID RES, V36, P2320
  • [35] Circulating activated platelets assist THP-1 monocytoid/endothelial cell interaction under shear stress
    Theilmeier, G
    Lenaerts, T
    Remacle, C
    Collen, D
    Vermylen, J
    Hoylaerts, MF
    [J]. BLOOD, 1999, 94 (08) : 2725 - 2734
  • [36] Identification of vascular endothelial genes differentially responsive to fluid mechanical stimuli: Cyclooxygenase-2, manganese superoxide dismutase, and endothelial cell nitric oxide synthase are selectively up-regulated by steady laminar shear stress
    Topper, JN
    Cai, JX
    Falb, D
    Gimbrone, MA
    [J]. PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1996, 93 (19) : 10417 - 10422
  • [37] Blood flow and vascular gene expression: fluid shear stress as a modulator of endothelial phenotype
    Topper, JN
    Gimbrone, MA
    [J]. MOLECULAR MEDICINE TODAY, 1999, 5 (01): : 40 - 46
  • [38] Laminar shear stress - Mechanisms by which endothelial cells transduce an atheroprotective force
    Traub, O
    Berk, BC
    [J]. ARTERIOSCLEROSIS THROMBOSIS AND VASCULAR BIOLOGY, 1998, 18 (05) : 677 - 685
  • [39] TRILLO AA, 1979, LAB INVEST, V41, P294
  • [40] Vora DK, 1997, CIRC RES, V80, P810