Blocking very late antigen-4 integrin decreases leukocyte entry and fatty streak formation in mice fed an atherogenic diet
| Autor: | Devendra K. Vora, Peggy T. Shih, Marie Luise Brennan, Judith A. Berliner, Mariano J. Elices, Mary C. Territo, Aldons J. Lusis, Dana Strahl |
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| Rok vydání: | 1999 |
| Předmět: |
medicine.medical_specialty
Integrins Physiology Arteriosclerosis Receptors Lymphocyte Homing Vascular Cell Adhesion Molecule-1 Peptide Biology Integrin alpha4beta1 Lesion chemistry.chemical_compound Mice In vivo Internal medicine medicine Leukocytes Oil Red O Animals Humans Receptor Aorta chemistry.chemical_classification Monocyte Fatty streak Lipid metabolism Lipid Metabolism Fibronectins Mice Inbred C57BL medicine.anatomical_structure Endocrinology chemistry Receptors LDL Immunology Female Rabbits medicine.symptom Cardiology and Cardiovascular Medicine |
| Zdroj: | Circulation research. 84(3) |
| ISSN: | 0009-7330 |
| Popis: | Abstract —Atherosclerotic lesion development is characterized by the recruitment of leukocytes, principally monocytes, to the vessel wall. Considerable interest has been focused on the adhesion molecule(s) involved in leukocyte/endothelial interactions. The goal of the present study was to determine the role of the very late antigen-4 (VLA-4) integrin/ligand interaction in fatty streak development using murine models. Because α4 null mice are not viable, a peptidomimetic was used to block VLA-4–mediated leukocyte binding. The ability of a synthetic peptidomimetic of connecting segment-1 (CS-1 peptide) to block the recruitment of leukocytes and the accumulation of lipid in the aortic sinus of either wild-type mice (strain C57BL/6J) or mice with a low-density lipoprotein null mutation (LDLR−/−) maintained on an atherogenic diet was assessed. The active (Ac) CS-1 peptide or scrambled (Sc) CS-1 peptide was delivered subcutaneously into mice using a mini osmotic pump. Mice were exposed to the peptide for 24 to 36 hours before the onset of the atherogenic diet. In C57BL/6J mice, leukocyte entry into the aortic sinus, as assessed by en face preparations, was inhibited by the active peptide (Ac=28±4, Sc=54±6 monocytes/valve; P =0.004). Additionally, frozen sections stained with Oil Red O were analyzed to assess lipid accumulation in the aortic sinus. C57BL/6J mice that received the (Ac) compound demonstrated significantly reduced lesion areas as compared with mice that received the (Sc) peptide (Ac=4887±4438 μm 2 , Sc=15 009 ±5619 μm 2 ; P |
| Databáze: | OpenAIRE |
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