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  • Poster presentation
  • Open Access

P-selectin, an important mediator of angiogenesis in females: the role of estradiol

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Arthritis Res Ther20046 (Suppl 3) :95

  • Published:


  • Corneal Endothelial Cell
  • Protein Kinase Pathway
  • Human Dermal Microvascular Endothelial Cell
  • Matrigel Plug
  • Gene Deficient Mouse

Angiogenesis, or new blood vessel formation, is key in vasculoproliferative disorders including rheumatoid arthritis. Here we report that the mediation of angiogenesis by P-selectin, an important member of the selectin adhesion molecule family, is unexpectedly sex dependent. In vivo angiogenesis measured in a Matrigel plug, in a sponge granuloma, and in a corneal micropocket was consistently impaired in P-selectin gene deficient mice compared with wild-type mice, but only if the P-selectin-deficient mice were female. Estrogen appeared to be one significant mediator of P-selectin sensitivity. In vitro the chemotactic activity of soluble P-selectin for human dermal microvascular endothelial cells was augmented by 17β-estradiol (E2). Conversely, an antibody blockade of P-selectin reduced E2-induced sprout formation in female mouse corneal endothelial cell morphogenesis assays, inhibited E2-induced endothelial cell signaling via the Src and mitogen-activated protein kinase pathways, and decreased E2-induced secretion of angiogenic basic fibroblast growth factor. In addition to its classical roles in leucocyte extravasation, P-selectin may also contribute to a variety of inflammatory diseases as a sex-restricted angiogenic intermediary.

Authors’ Affiliations

Department of Internal Medicine, University of Michigan Medical School, Ann Arbor, Michigan, USA
VA Ann Arbor Healthcare System, Ann Arbor, Michigan, USA
Department of Urology, Northwestern University Medical School, Chicago, Illinois, USA
Department of Medicine, Northwestern University Medical School, Chicago, Illinois, USA


© The Author(s) 2004