Erschienen in:
01.09.2004 | Poster presentation
P-selectin, an important mediator of angiogenesis in females: the role of estradiol
verfasst von:
AE Koch, OV Volpert, MV Volin, JM Woods, JH Ruth, CC Park, MA Amin
Erschienen in:
Arthritis Research & Therapy
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Sonderheft 3/2004
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Excerpt
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. …