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(Circulation. 2009;119:547-557.)
© 2009 American Heart Association, Inc.

Molecular Cardiology

Endothelial Progenitor Cells Restore Renal Function in Chronic Experimental Renovascular Disease

Alejandro R. Chade, MD^*; Xiangyang Zhu, MD, PhD^*; Ronit Lavi, MD; James D. Krier, MS; Sorin Pislaru, MD; Robert D. Simari, MD; Claudio Napoli, MD, PhD; Amir Lerman, MD; Lilach O. Lerman, MD, PhD

From the Department of Internal Medicine (Divisions of Nephrology and Hypertension [A.R.C., X.Z., R.L., J.D.K., L.O.L.] and Cardiovascular Diseases [S.P., R.D.S., A.L., L.O.L.]), Mayo Clinic, Rochester, Minn, and Department of General Pathology and Excellence Research Center of Cardiovascular Diseases, School of Medicine, II University of Naples, Naples, Italy (C.N.). A.R.C. is currently at the Department of Physiology and Biophysics, University of Mississippi Medical Center, Jackson. Dr Lavi is currently at the Department of Anesthesia and Perioperative Medicine, London Health Care Science Centre, University of Western Ontario, London, Ontario, Canada.

Correspondence to Lilach O. Lerman, MD, PhD, Division of Nephrology and Hypertension, Mayo Clinic, 200 First St SW, Rochester, MN 55905. E-mail Lerman.Lilach{at}Mayo.Edu

Received April 25, 2008; accepted November 24, 2008.

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.

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CLINICAL PERSPECTIVE

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Circulation 2009 119: 487-488. [Extract] [Full Text]