title: Renal ischemia-reperfusion induces release of angiopoietin-2 from human grafts of living and deceased donors.
abstract: BACKGROUND
  Recent insights suggest that endothelial cell (EC) activation plays a major role in renal ischemia-reperfusion (I/R) injury. Interactions between ECs and pericytes via signaling molecules, including angiopoietins, are involved in maintenance of the vascular integrity. Experimental data have shown that enhancement of Angiopoietin (Ang)-1 signaling might be beneficial in renal I/R injury. However, little is known about the role of angiopoietins in human renal I/R injury.
  
  
  METHODS
  In this study, EC activation and changes in angiopoeitins are assessed in human living-donor (LD) and deceased-donor (DD) kidney transplantation. Local release of angiopoietins was measured by unique, dynamic arteriovenous measurements over the reperfused kidney.
  
  
  RESULTS
  Renal I/R is associated with acute EC activation shown by a vast Ang-2 release from both LD and DD shortly after reperfusion. Its counterpart Ang-1 was not released. Histologic analysis of kidney biopsies showed EC loss after reperfusion. Baseline protein and mRNA Ang-1 expression was significantly reduced in DD compared with LD and declined further after reperfusion.
  
  
  CONCLUSIONS
  Human renal I/R injury induces EC activation after reperfusion reflected by Ang-2 release from the kidney. Interventions aimed at maintenance of vascular integrity by modulating angiopoietin signaling may be promising in human clinical kidney transplantation.
authors.affiliation: Department of Surgery, Leiden University Medical Center, Leiden, The Netherlands.
authors.forename: Dorottya K
authors.initials: DK
authors.lastname: de Vries
authors.forename: Meriem
authors.initials: M
authors.lastname: Khairoun
authors.forename: Jan H N
authors.initials: JH
authors.lastname: Lindeman
authors.forename: Ingeborg M
authors.initials: IM
authors.lastname: Bajema
authors.forename: Emile
authors.initials: E
authors.lastname: de Heer
authors.forename: Mark
authors.initials: M
authors.lastname: Roest
authors.forename: Anton J
authors.initials: AJ
authors.lastname: van Zonneveld
authors.forename: Cees
authors.initials: C
authors.lastname: van Kooten
authors.forename: Ton J
authors.initials: TJ
authors.lastname: Rabelink
authors.forename: Alexander F
authors.initials: AF
authors.lastname: Schaapherder
authors.forename: Marlies E J
authors.initials: ME
authors.lastname: Reinders
mesh_terms: D042683:Angiopoietin-1 / Q000502:physiology; D042702:Angiopoietin-2 / Q000502:physiology*; D006801:Humans; D007668:Kidney / Q000098:blood supply*; D016030:Kidney Transplantation; D019520:Living Donors; D015427:Reperfusion Injury / Q000503:physiopathology*; D014841:von Willebrand Factor / Q000502:physiology
chemical_list: D042683:Angiopoietin-1; D042702:Angiopoietin-2; D014841:von Willebrand Factor