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Please use this identifier to cite or link to this item: http://hdl.handle.net/1807/32920

Title: SLIT2/ROBO-1: Novel Modulators of Vascular Injury
Authors: Patel, Sajedabanu
Advisor: Robinson, Lisa
Department: Medical Science
Keywords: atherosclerosis
Issue Date: 4-Sep-2012
Abstract: In atherosclerosis, infiltrating leukocytes and vascular smooth muscle cells (VSMCs) cause progressive vascular narrowing. Platelet-mediated thrombosis ultimately causes complete vessel occlusion, resulting in heart attack or stroke. In animal models and human patients, individually blocking these events is only partially effective. Another therapeutic strategy would be to globally target these multiple cell types. Slit proteins act as developmental neuronal repellents, and Slit2 via interaction with its receptor, Robo-1, impairs inflammatory recruitment of leukocytes and VSMCs. We detected Robo-1 expression in human and murine platelets. Using static and shear assays, we demonstrate that Slit2 impaired platelet adhesion and spreading on fibrinogen, fibronectin and collagen. Slit2 mediated these effects, in part, by suppressing activation of Akt but not Rac1, Cdc42, Erk or p38 MAPK. Slit2 also prevented ADP-mediated granular secretion. In mouse tail-bleeding experiments, Slit2 dose-dependently prolonged bleeding times in vivo. These data suggest a therapeutic role of Slit2 in atherothrombosis.
URI: http://hdl.handle.net/1807/32920
Appears in Collections:Master

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