title: Angiopoietin-1 mediates inhibition of hypertension-induced release of angiopoietin-2 from endothelial cells.
abstract: OBJECTIVE
  Adequate endothelial cell stimulation is a prerequisite for the adaptive remodelling of macro- and microvessels. 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, thus sensitizing the endothelial cells to pro-angiogenic and/or pro-inflammatory stimuli. Based on the observation that hypertension in mice reduces the abundance of Ang-2 stored in arterial endothelial cells, this study was aimed at testing the hypothesis that an increase in wall stress (WS) or stretch-a hallmark of hypertension-is sufficient to release Ang-2 from endothelial cells.
  
  
  RESULTS
  In fact, stretching of isolated perfused mouse arteries or human cultured endothelial cells rapidly elicited an increased release of Ang-2. In the cultured endothelial cells, this was preceded by a transient rise in intracellular free calcium, abrogated through calcium chelation and accompanied by a decrease in Tie-2 phosphorylation. Interestingly, Ang-1 abolished the stretch-induced release of Ang-2 from both cultured and native endothelial cells through inhibiting the stretch-dependent mobilization of intracellular calcium.
  
  
  CONCLUSIONS
  Collectively, these results indicate that increased WS or stretch facilitates the release of Ang-2 from endothelial cell Weibel-Palade bodies, and that Ang-1 can block this by attenuating the stretch-mediated rise in intracellular calcium.
authors.affiliation: Division of Cardiovascular Physiology,  Institute of Physiology and Pathophysiology, University of Heidelberg, Im Neuenheimer Feld 326, 69120 Heidelberg,  Germany.
authors.forename: Thomas
authors.initials: T
authors.lastname: Korff
authors.forename: Evelyn
authors.initials: E
authors.lastname: Ernst
authors.forename: Rainer
authors.initials: R
authors.lastname: Nobiling
authors.forename: Anja
authors.initials: A
authors.lastname: Feldner
authors.forename: Yvonne
authors.initials: Y
authors.lastname: Reiss
authors.forename: Karl H
authors.initials: KH
authors.lastname: Plate
authors.forename: Ulrike
authors.initials: U
authors.lastname: Fiedler
authors.forename: Hellmut G
authors.initials: HG
authors.lastname: Augustin
authors.forename: Markus
authors.initials: M
authors.lastname: Hecker
mesh_terms: D042683:Angiopoietin-1 / Q000494:pharmacology*; D042702:Angiopoietin-2 / Q000378:metabolism*; D000818:Animals; D002118:Calcium / Q000378:metabolism; D002478:Cells, Cultured; D042783:Endothelial Cells / Q000378:metabolism*; D004730:Endothelium, Vascular / Q000166:cytology / Q000378:metabolism*; D006801:Humans; D006973:Hypertension / Q000503:physiopathology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D042787:Receptor, TIE-2 / Q000378:metabolism
chemical_list: D042683:Angiopoietin-1; D042702:Angiopoietin-2; D042787:Receptor, TIE-2; D002118:Calcium