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Hypertension‐induced endothelial cell angiopoietin‐2 release is inhibited by angiopoietin‐1
Author(s) -
Korff Thomas,
Ernst Evelyn,
Nobiling Rainer,
Feldner Anja,
Reiss Yvonne,
Plate Karl H,
Fiedler Ulrike,
Augustin Hellmut G,
Hecker Markus
Publication year - 2012
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.26.1_supplement.1058.3
Subject(s) - microbiology and biotechnology , autocrine signalling , chemistry , endothelial stem cell , calcium , angiopoietin , receptor , paracrine signalling , endocrinology , calcium in biology , endothelium , medicine , context (archaeology) , intracellular , in vitro , biology , biochemistry , vascular endothelial growth factor , vegf receptors , paleontology , organic chemistry
A pivotal autocrine mechanism following endothelial cell activation is the release of angiopoietin‐2 (Ang‐2) which subsequently antagonizes the binding of Ang‐1 to the Tie‐2 receptor. In this context, we noted that hypertension in mice reduces the abundance of Ang‐2 stored in arterial endothelial cells and hypothesized that this Ang‐2 release depends on an increase in circumferential wall tension or stretch – a hallmark of hypertension. In fact, stretching isolated perfused mouse arteries or human cultured endothelial cells triggered rapid Ang‐2 release in a calcium‐dependent manner. Interestingly, Ang‐1 abolished stretch‐induced Ang‐2 release both in the isolated perfused mouse arteries and in the cultured endothelial cells. Subsequent analyses of the latter indicated that pre‐treatment with Ang‐1 robustly inhibits their stretch‐induced calcium response as well as the stretch‐mediated expression of pro‐inflammatory adhesion molecules. Collectively, our results suggest that stretch induces the release of Ang‐2 from human cultured endothelial cells and that Ang‐1 counteracts these Ang‐2 functions by attenuating the stretch‐dependent intracellular calcium release which may at least in part explain its anti‐inflammatory effect in stretch‐stimulated endothelial cells.