The Cell Motility Modulator Slit2 Is a Potent Inhibitor of Platelet Function

• DOI: 10.1161/circulationaha.112.105452
• Publication Date: 2012-08-04T04:58:16Z
• Authors: Sajedabanu Patel; Yi-Wei Huang; Adili Reheman; Fred G. Pluthero; Swasti Chaturvedi; Ilya M. Mukovozov; Soumitra Tole; Guang-Ying Liu; Ling Li; Yves Durocher; Heyu Ni; Walter H.A. Kahr; Lisa A. Robinson
• Keywords: Blood Platelets; Male; blood platelets; Roundabout Proteins; 610; Nerve Tissue Proteins; Ferric Compounds; Mice; 03 medical and health sciences; Platelet Adhesiveness; Chlorides; Cell Movement; Risk Factors; 616; Animals; Humans; Carotid Artery Thrombosis; Receptors, Immunologic; thrombosis; Cells, Cultured; 0303 health sciences; 3. Good health; Mice, Inbred C57BL; Models, Animal; Intercellular Signaling Peptides and Proteins; blood cells

Vascular injury and atherothrombosis involve vessel infiltration by inflammatory leukocytes, migration of medial vascular smooth muscle cells to the intimal layer, ultimately acute thrombosis. A strategy simultaneously target these pathological processes has yet be identified. The secreted protein, Slit2, its transmembrane receptor, Robo-1, repel neuronal in developing central nervous system. More recently, it been appreciated that Slit2 impairs chemotaxis leukocytes toward diverse attractants. effects on platelet function thrombus formation have never explored.We detected Robo-1 expression human murine platelets megakaryocytes confirmed presence via immunofluorescence microscopy flow cytometry. In both static shear microfluidic assays, impaired adhesion spreading extracellular matrix substrates suppressing activation Akt. also prevented exposure ADP. vivo studies, prolonged bleeding times tail assays. Using intravital microscopy, we found after mesenteric arteriolar carotid artery injury, delayed occlusion time stable occlusive thrombi.These data demonstrate is a powerful negative regulator formation. ability block multiple events may allow effectively prevent treat thrombotic disorders such as myocardial infarction stroke.