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 and pericyte/EC interactions in human renal I/R injury. In this study, EC activation and changes in pericytes and angiopoeitins are assessed in human living and deceased donor kidney transplantation. Local release of angiopoietins was measured by unique, dynamic arteriovenous measurements over the reperfused kidney. Results demonstrate that renal I/R is associated with acute EC activation shown by a vast Ang-2 release from both living and deceased donors shortly after reperfusion. Its counterpart Ang-1 was not released. Histological analysis of kidney biopsies showed EC loss, accompanied by diminished NG2 pericyte expression after reperfusion. Baseline protein and mRNA Ang-1 expression was significantly reduced in deceased compared to living donors and decreased after reperfusion. Interventions aimed at maintenance of vascular integrity by Ang-2 blockade or Ang-1 administration may provide a tool for donor pretreatment and interventions around human clinical transplantation.

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