Localized reduction of atherosclerosis in von Willebrand factor-deficient mice
| Autor: | Maria Economopoulos, Nassia Methia, Denisa D. Wagner, Patrick Andre, Cécile V. Denis |
|---|---|
| Rok vydání: | 2001 |
| Předmět: |
Male
P-selectin Arteriosclerosis Saturated fat Ligands Biochemistry Mice hemic and lymphatic diseases Leukocytes Platelet Mesenteric arteries Aorta Mice Knockout biology Chemistry Integrin beta3 Hematology Chemotaxis Leukocyte von Willebrand Diseases medicine.anatomical_structure cardiovascular system Female medicine.symptom circulatory and respiratory physiology congenital hereditary and neonatal diseases and abnormalities medicine.medical_specialty Endothelium Immunology Aortic Diseases Platelet Membrane Glycoproteins Lesion Von Willebrand factor Antigens CD medicine.artery Internal medicine von Willebrand Factor medicine Cell Adhesion Animals Genetic Predisposition to Disease Crosses Genetic Cell Biology Sinus of Valsalva Mice Inbred C57BL Endocrinology Receptors LDL biology.protein Diet Atherogenic |
| Zdroj: | Blood. 98(5) |
| ISSN: | 0006-4971 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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