Angiopoietin-1 treated early endothelial outgrowth cells (eEOCs) are activated in vitro and reduce renal damage in murine acute ischemic kidney injury (iAKI)

摘要

Background Acute kidney injury (AKI) severely worsens prognosis of hospitalized patients. Early Endothelial Outgrowth Cells act protective in murine acute ischemic renal failure and renoprotective actions of eEOCs have been documented to increase after cell pretreatment with 8-O-cAMP and Melatonin. Angiopoietin-1 is critically involved in maintaining vascular integrity and regeneration. Aim of the study was to analyze the consequences of eEOC treatment with Ang-1 in murine AKI. Methods After 40?minutes of unilateral renal artery clamping with contralateral nephrectomy, male C57/Bl6N mice were injected with either untreated or pretreated (Ang-1) syngeneic murine eEOCs. Two days later serum creatinine levels and morphology were evaluated. Cultured, Ang-1 treated murine eEOCs were analyzed for production/release of proangiogenic and proinflammatory mediators, migratory activity, and cell survival, respectively. Results Angiopoietin-1 pretreatment of eEOCs significantly reduced serum creatinine in cell-injected mice. In vitro analysis showed increased migration of Ang-1 treated eEOCs and supernatant from Ang-1 treated eEOCs stimulated migration of cultured mature endothelial cells. In addition, Ang-1 reduced percentages of Annexin V+/PI+ eEOCs. Intrarenal numbers of eEOCs remained unaffected by Ang-1 and eEOCs did not produce more or less proangiogenic/proinflammatory mediators after being stimulated with Ang-1. Conclusions Angiopoietin-1 pretreatment of eEOCs increases the cells’ renoprotective competence in ischemic AKI. Thus, the armentarium of eEOC agonists in AKI is increasingly being expanded and the treatment of AKI with eEOCs becomes a promising future option.