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Differential effects of a bradykinin receptor 2 (B2R) and bradykinin receptor 1 (B1R) in vasculogenesis of human endothelial progenitor cells (EPCs) compared to human umbilical vein endothelial cells (HUVECs)
Author(s) -
Bakdash Nadia,
Wu Yi,
Colman Robert
Publication year - 2010
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.24.1_supplement.750.14
Subject(s) - vasculogenesis , bradykinin , umbilical vein , progenitor cell , chemistry , antagonist , receptor , endocrinology , microbiology and biotechnology , medicine , stem cell , biology , in vitro , biochemistry
Bradykinin (BK), a potent activator of endothelial cells, is known to induce vasodilation and vascular permeability. BK signaling is initiated by binding to G protein‐coupled receptors B2R and/or B1R. B2R is constitutively expressed in endothelial cells while B1R is upregulated by inflammatory stimuli. We now report that EPCs undergo differentiation (tube formation) in a 3D collagen gel. Pre‐incubation of EPCs with a B2R selective antagonist (HOE‐140) reduced differentiation (p<0.001). We found that EPCs stimulated with the selective B2R agonist FR190997 (50 nM) enhanced migration, a response abrogated by HOE‐140 (p<0.05). We conclude that EPCs utilize B2R for vasculogenesis and migration. In contrast, HUVECs did not display a significant reduction in vasculogenesis upon addition of exogenous BK. After pre‐incubation with [des‐Arg 10 ]‐HOE 140, (B1R selective antagonist), BK‐stimulated HUVECs displayed a reduction in tube formation (p<0.001), suggesting that HUVECs utilize B1R for vasculogenesis. In the presence of the B1R antagonist, BK‐stimulated HUVEC migration was inhibited (p<0.01). In addition, proliferation of HUVECs remained unchanged upon stimulation with BK. Upon exposure to the B1R antagonist, proliferation was unchanged. In conclusion, in BK‐stimulated EPCs, B2R mediates differentiation and migration. In contrast, in BK‐stimulated HUVECs, the B1R antagonist selectively inhibits vasculogenesis and migration but not proliferation.