Deficiency of P-selectin Glycoprotein Ligand-1 is Protective against the Prothrombotic Effects of Interleukin-1β
| Autor: | Daniel T. Eitzman, Wei Luo, Hui Wang, Chiao Guo, Jintao Wang, Kyle Kleiman |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2015 |
| Předmět: |
Male
P-selectin Carotid Artery Common Interleukin-1beta Down-Regulation Inflammation Article Proinflammatory cytokine medicine Animals Genetic Predisposition to Disease Neutralizing antibody Blood Coagulation Whole blood Mice Knockout Membrane Glycoproteins integumentary system biology business.industry Carotid Artery Thrombosis Thrombosis Hematology medicine.disease Mice Inbred C57BL Disease Models Animal P-Selectin Phenotype Immunology biology.protein P-selectin glycoprotein ligand-1 medicine.symptom business Carotid Artery Injuries |
| Popis: | Summary Background Proinflammatory cytokines are associated with cardiovascular diseases, including acute and recurrent myocardial infarction. However, the causal role of cytokines in thrombotic complications of atherosclerosis remains unclear. Interleukin-1β (IL-1β) is currently being targeted in a human clinical trial for the prevention of ischemic events. Objectives The purpose of the present study was to test the role of IL-1β in arterial thrombosis and a potential protective effect of P-selectin glycoprotein ligand-1 (Psgl-1) deficiency. Methods and results Wild-type and Psgl-1–deficient mice were treated with IL-1β and then subjected to carotid photochemical injury to induce thrombosis. IL-1β shortened the time to thrombosis in wild-type mice, while Psgl-1−/− mice were protected from the prothrombotic effects of IL-1β. A neutralizing antibody to Psgl-1 was also effective in protecting against the prothrombotic effects of IL-1β. The protective effect of Psgl-1 deficiency was associated with reduced plasma levels of soluble P-selectin and collagen-stimulated whole blood aggregation. Conclusions Our data demonstrate that Psgl-1 deficiency is protective against the prothrombotic effects of IL-1β and suggest that Psgl-1 inhibition may be a useful treatment strategy for targeting vascular thrombosis associated with enhanced inflammatory states. |
| Databáze: | OpenAIRE |
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