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Rolling and adhesion of monocytes to early atherosclerotic lesions of apolipoprotein E-/-(apoE-/-) mice requires P-selectin, PSGL-1, α4 integrin and VCAM-1

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3 Author(s)
Yuqing Huo ; Dept. of Biomed. Eng., Univ. of Virginia Health Sci. Center, Charlottesville, VA, USA ; C. L. Ramos ; K. Ley

To investigate the molecular basis of mononuclear cell rolling and adhesions to vascular endothelium prone to develop atherosclerotic lesion, isolated carotid arteries from ApoE-/- and other relevant mice were perfused under physiological shear stress conditions. Carotid arteries from 10-12 weeks old ApoE-/- and C57BL/6 wide-type mice fed a Western diet for 4-5 weeks, representing early atherosclerotic lesions according to vessel histology, supported mononuclear cell (U937) attachment, rolling and adhesion, while carotid arteries from an atherosclerosis-resistant strain (BALB/C) showed no adhesion. Antibody blocking assays showed that mononuclear rolling and adhesion were significantly inhibited by treating the vessel with P-selectin antibody or treating U937 with anti-PSGL-1. Treating the vessel with VCAM-1 antibody or treating U937 with α4β1 integrin antibody caused rolling velocities to increase (from 86±4 to 167±7 μm/s). This suggests that mononuclear cell can attach, roll and adhere on early atherosclerotic endothelium via the P-selectin-PSGL-1 and VCAM-1-α4β1 pathways

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[Engineering in Medicine and Biology, 1999. 21st Annual Conference and the 1999 Annual Fall Meetring of the Biomedical Engineering Society] BMES/EMBS Conference, 1999. Proceedings of the First Joint  (Volume:1 )

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