title: Deficiency of P-selectin glycoprotein ligand-1 is protective against the prothrombotic effects of interleukin-1β.
abstract: 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.
  
  
  OBJECTIVE
  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.
  
  
  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.
authors.affiliation: Department of Internal Medicine, Cardiovascular Research Center, University of Michigan, Ann Arbor, MI, USA.
authors.forename: H
authors.initials: H
authors.lastname: Wang
authors.affiliation: Department of Internal Medicine, Cardiovascular Research Center, University of Michigan, Ann Arbor, MI, USA.
authors.forename: K
authors.initials: K
authors.lastname: Kleiman
authors.affiliation: Department of Internal Medicine, Cardiovascular Research Center, University of Michigan, Ann Arbor, MI, USA.
authors.forename: J
authors.initials: J
authors.lastname: Wang
authors.affiliation: Department of Internal Medicine, Cardiovascular Research Center, University of Michigan, Ann Arbor, MI, USA.
authors.forename: W
authors.initials: W
authors.lastname: Luo
authors.affiliation: Department of Internal Medicine, Cardiovascular Research Center, University of Michigan, Ann Arbor, MI, USA.
authors.forename: C
authors.initials: C
authors.lastname: Guo
authors.affiliation: Department of Internal Medicine, Cardiovascular Research Center, University of Michigan, Ann Arbor, MI, USA.
authors.forename: D T
authors.initials: DT
authors.lastname: Eitzman
mesh_terms: D000818:Animals; D001777:Blood Coagulation; D020212:Carotid Artery Injuries / Q000150:complications*; D017536:Carotid Artery, Common / Q000378:metabolism / Q000473:pathology; D004195:Disease Models, Animal; D015536:Down-Regulation; D020022:Genetic Predisposition to Disease; D053583:Interleukin-1beta; D008297:Male; D008562:Membrane Glycoproteins / Q000172:deficiency*; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D019007:P-Selectin / Q000097:blood; D010641:Phenotype; D013927:Thrombosis / Q000139:chemically induced / Q000235:genetics / Q000378:metabolism / Q000517:prevention & control*
chemical_list: D053583:Interleukin-1beta; D008562:Membrane Glycoproteins; D019007:P-Selectin; C084882:P-selectin ligand protein
keywords: carotid artery thrombosis; cytokines; inflammation; platelet aggregation; rose bengal