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Spleen tyrosine kinase mediates angiotensin II‐ and vascular endothelial growth factor‐induced angiogenesis
Author(s) -
Buharalioglu Cuneyt Kemal,
Yaghini Fariborz A,
Song Chi Young,
Ghafoor Hafiz U,
Estes Anne M,
Malik Kafait U
Publication year - 2009
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.23.1_supplement.625.9
Subject(s) - angiogenesis , syk , vascular endothelial growth factor , angiotensin ii , matrigel , sprouting angiogenesis , tyrosine kinase , chemistry , kinase insert domain receptor , cancer research , neovascularization , endocrinology , microbiology and biotechnology , vascular endothelial growth factor a , medicine , biology , signal transduction , receptor , vegf receptors
Angiotensin II (AngII) and vascular endothelial growth factor (VEGF) stimulate angiogenesis. A 72 kDa non‐receptor tyrosine kinase, spleen tyrosine kinase (Syk) expressed in endothelial cells has been implicated in their migration and proliferation and in vasculogenesis. Syk also mediates AngII‐induced vascular smooth muscle cell hypertrophy. This study was conducted to determine the contribution of Syk to the angiogenic effect of AngII and VEGF. Angiogenesis was determined in Matrigel by tube formation from endothelial cells EA.hy926, and sprouting of rat aortic rings into microvessels . EA.hy926 cells were allowed to form tubular structures for 16 h and aortic rings to sprout into microvessel for 5 days and then phase contrast images were recorded. Both tube length and numbers were calculated. AngII (10 nM) and VEGF (50 ng/ml) stimulated EA.hy926 cells to organize into tubular network and increased aortic sprouting. The effect of VEGF but not AngII to stimulate tube formation and aortic sprouting was inhibited by VEGFR2 blocker SU1498 (10 µM). Both AngII‐ and VEGF‐induced angiogenesis and Syk phosphorylation, as determined by Western blot analysis, was inhibited by piceatannol (10 µM), a Syk kinase inhibitor. These data suggest that AngII‐induced angiogenesis is independent of VEGFR2 phosphorylation and that both AngII‐ and VEGF‐induced angiogenesis is mediated by Syk.