Endothelial progenitor cells restore renal function in chronic experimental renovascular disease

Alejandro R. Chade, Xiangyang Zhu, Ronit Lavi, James D. Krier, Sorin Pislaru, Robert D. Simari, Claudio Napoli, Amir Lerman, Lilach O. Lerman

Research output: Contribution to journalArticle

171 Scopus citations

Abstract

Background - Endothelial progenitor cells (EPCs) promote neovascularization and endothelial repair. Renal artery stenosis (RAS) may impair renal function by inducing intrarenal microvascular injury and remodeling. We investigated whether replenishment with EPCs would protect the renal microcirculation in chronic experimental renovascular disease. Methods and Results - Single-kidney hemodynamics and function were assessed with the use of multidetector computed tomography in vivo in pigs with RAS, pigs with RAS 4 weeks after intrarenal infusion of autologous EPCs, and controls. Renal microvascular remodeling and angiogenic pathways were investigated ex vivo with the use of micro-computed tomography, histology, and Western blotting. EPCs increased renal expression of angiogenic factors, stimulated proliferation and maturation of new vessels, and attenuated renal microvascular remodeling and fibrosis in RAS. Furthermore, EPCs normalized the blunted renal microvascular and filtration function. Conclusions - The present study shows that a single intrarenal infusion of autologous EPCs preserved microvascular architecture and function and decreased microvascular remodeling in experimental chronic RAS. It is likely that restoration of the angiogenic cascade by autologous EPCs involved not only generation of new vessels but also acceleration of their maturation and stabilization. This contributed to preserving the blood supply, hemodynamics, and function of the RAS kidney, supporting EPCs as a promising therapeutic intervention for preserving the kidney in renovascular disease.

Original languageEnglish (US)
Pages (from-to)547-557
Number of pages11
JournalCirculation
Volume119
Issue number4
DOIs
StatePublished - Feb 3 2009

Keywords

  • Blood flow
  • Hypertension
  • Kidney
  • Progenitor cells
  • Renal
  • Renal artery stenosis

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine
  • Physiology (medical)

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