title: 17beta-estradiol increases volume, apical surface and elasticity of human endothelium mediated by Na+/H+ exchange.
abstract: OBJECTIVE
  17beta-estradiol is known to delay the onset of atherosclerosis in women but cellular mechanisms are still unclear. Estrogens bind to specific receptors and initiate a signaling cascade that involves the activation of plasma membrane Na(+)/H(+) exchange. We hypothesized that estrogens interfere with ion transport across the plasma membrane and thus control endothelial structure and function. Therefore, we investigated the effects of the sex steroids 17beta-estradiol, progesterone, and testosterone on volume, apical surface and elasticity in human endothelium.
  
  
  METHODS
  The atomic force microscope was used as an imaging tool and as an elasticity sensor. We applied the antiestrogen tamoxifen, the Na(+)/H(+) exchange blocker cariporide and the epithelial Na(+)channel blocker amiloride to elucidate the role of transmembrane ion transport in hormone-treated human umbilical vein endothelial cells (HUVEC).
  
  
  RESULTS
  Incubation with 17beta-estradiol for 72 h led to a dose-dependent increase of endothelial cell volume (41%), apical cell surface (22%), and cell elasticity (53%) as compared to non-17beta-estradiol treated controls. Block of the 17beta-estradiol receptor by tamoxifen and of plasma membrane Na(+)/H(+) exchange by cariporide prevented the hormone-induced changes. Progesterone and testosterone were ineffective.
  
  
  CONCLUSIONS
  17beta-estradiol increases HUVEC water content and HUVEC elasticity mediated by activated estrogen receptors. The estrogen response depends on the activation of plasma membrane Na(+)/H(+) exchange. The increase in endothelial cell elasticity could be one of the vasoprotective mechanisms postulated for 17beta-estradiol.
authors.affiliation: Department of Internal Medicine D, University of Muenster, Germany. hillebu@uni-muenster.de
authors.forename: U
authors.initials: U
authors.lastname: Hillebrand
authors.forename: M
authors.initials: M
authors.lastname: Hausberg
authors.forename: C
authors.initials: C
authors.lastname: Stock
authors.forename: V
authors.initials: V
authors.lastname: Shahin
authors.forename: D
authors.initials: D
authors.lastname: Nikova
authors.forename: C
authors.initials: C
authors.lastname: Riethmüller
authors.forename: K
authors.initials: K
authors.lastname: Kliche
authors.forename: T
authors.initials: T
authors.lastname: Ludwig
authors.forename: H
authors.initials: H
authors.lastname: Schillers
authors.forename: S W
authors.initials: SW
authors.lastname: Schneider
authors.forename: H
authors.initials: H
authors.lastname: Oberleithner
mesh_terms: D000584:Amiloride / Q000494:pharmacology; D002462:Cell Membrane / Q000378:metabolism; D048429:Cell Size / Q000187:drug effects; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D004548:Elasticity; D042783:Endothelial Cells / Q000187:drug effects / Q000378:metabolism*; D004958:Estradiol / Q000494:pharmacology*; D020847:Estrogen Receptor Modulators / Q000494:pharmacology; D006146:Guanidines / Q000494:pharmacology; D006801:Humans; D018625:Microscopy, Atomic Force; D011374:Progesterone / Q000494:pharmacology; D026941:Sodium Channel Blockers / Q000494:pharmacology; D017923:Sodium-Hydrogen Exchangers / Q000037:antagonists & inhibitors / Q000378:metabolism*; D013450:Sulfones / Q000494:pharmacology; D013629:Tamoxifen / Q000494:pharmacology; D013739:Testosterone / Q000494:pharmacology
chemical_list: D020847:Estrogen Receptor Modulators; D006146:Guanidines; D026941:Sodium Channel Blockers; D017923:Sodium-Hydrogen Exchangers; D013450:Sulfones; D013629:Tamoxifen; D013739:Testosterone; D011374:Progesterone; D004958:Estradiol; D000584:Amiloride; C093373:cariporide