Glucocorticoid-mediated inhibition of angiogenic changes in XXXX endothelial cells is not caused by reductions in cell proliferation or migration.

@entity1 @entity1603 @entity4738 @entity7 @entity22667 @entity619 @entity701 @entity3927 @entity855 @entity2383
BACKGROUND: Glucocorticoid-mediated inhibition of angiogenesis is important in physiology, pathophysiology and therapy. However, the mechanisms through which glucocorticoids inhibit growth of new blood vessels have not been established. This study addresses the hypothesis that physiological levels of glucocorticoids inhibit angiogenesis by directly preventing tube formation by endothelial cells. METHODOLOGY/PRINCIPAL FINDINGS: Cultured @entity1 umbilical vein (HUVEC) and aortic (HAoEC) endothelial cells were used to determine the influence of glucocorticoids on @entity2383 ( @entity2383 ) formation, and on cellular proliferation ( @entity1603 ( @entity1603 ) incorporation), viability ( @entity855 production) and migration (Boyden chambers). @entity619 or @entity701 (at physiological concentrations) inhibited both basal and @entity22667 (PGF(2a))-induced and @entity7 ( @entity7 ) stimulated @entity2383 formation in endothelial cells (ECs) cultured on Matrigel, effects which were blocked with the @entity4738 antagonist @entity3927 . Glucocorticoids had no effect on EC viability, migration or proliferation. Time-lapse imaging showed that @entity701 blocked @entity7 -stimulated cytoskeletal reorganisation and initialisation of tube formation. Real time PCR suggested that increased expression of thrombospodin-1 contributed to glucocorticoid-mediated inhibition of @entity2383 formation. CONCLUSIONS/SIGNIFICANCE: We conclude that glucocorticoids interact directly with glucocorticoid receptors on vascular ECs to inhibit @entity2383 formation. This action, which was conserved in ECs from two distinct vascular territories, was due to alterations in cell morphology rather than inhibition of EC viability, migration or proliferation and may be mediated in part by induction of thrombospodin-1. These findings provide important insights into the anti-angiogenic action of endogenous glucocorticoids in health and disease.
