Endothelial Progenitor Cells Restore Renal Function in Chronic Experimental Renovascular Disease

• Published in: Circulation (New York, N.Y.) Vol. 119; no. 4; pp. 547 - 557
• Main Authors: CHADE, Alejandro R, XIANGYANG ZHU, LAVI, Ronit, KRIER, James D, PISLARU, Sorin, SIMARI, Robert D, NAPOLI, Claudio, LERMAN, Amir, LERMAN, Lilach O
• Format: Journal Article
• Language: English
• Published: Hagerstown, MD Lippincott Williams & Wilkins 03.02.2009
• Subjects: Angiography; Animals; Biological and medical sciences; Blood and lymphatic vessels; Blood vessels and receptors; Cardiology. Vascular system; Chronic Disease; Diseases of the peripheral vessels. Diseases of the vena cava. Miscellaneous; Endothelial Cells - cytology; Fundamental and applied biological sciences. Psychology; Hematopoietic Stem Cell Transplantation; Hematopoietic Stem Cells - cytology; Hypertension, Renal - diagnostic imaging; Hypertension, Renal - pathology; Hypertension, Renal - therapy; Medical sciences; Microcirculation - physiology; Neovascularization, Physiologic - physiology; Recovery of Function; Renal Artery Obstruction - diagnostic imaging; Renal Artery Obstruction - pathology; Renal Artery Obstruction - therapy; Renal Circulation - physiology; Sus scrofa; Tomography, X-Ray Computed; Vertebrates: cardiovascular system; Kidney disease; Hypertension; Endothelial cell; Urinary system disease; Cardiovascular disease; progenitor cells; Chronic kidney disease; Blood flow; Arterial disease; Vascular disease; kidney; Renal failure; Hemodynamics; hypertension, renal; Renal artery stenosis; Renal artery disease; Progenitor cell
• ISSN: 0009-7322; 1524-4539
• DOI: 10.1161/CIRCULATIONAHA.108.788653

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. 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. 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.