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.

journal_name

Transplantation

journal_title

Transplantation

authors

de Vries DK,Khairoun M,Lindeman JH,Bajema IM,de Heer E,Roest M,van Zonneveld AJ,van Kooten C,Rabelink TJ,Schaapherder AF,Reinders ME

doi

10.1097/TP.0b013e31829854d5

subject

Has Abstract

pub_date

2013-08-15 00:00:00

pages

282-9

issue

3

eissn

0041-1337

issn

1534-6080

journal_volume

96

pub_type

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