on July 20, 2006
Published online before print July 20, 2006, doi: 10.1161/01.ATV.0000237750.44469.88
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Submitted on May 11, 2006
Accepted on June 27, 2006
Number and Function of Endothelial Progenitor Cells as a Marker of Severity for Diabetic Vasculopathy
Gian Paolo Fadini MD*;
From the Department of Clinical and Experimental Medicine (G.P.F., E.M., S.V.d.K, A.T., A.A.), Division of Metabolic Diseases, University of Padova, School of Medicine, Italy; the Department of Biomedical Sciences (S.S., M.A.), University of Padova, Medical School, Italy; the Department of Clinical and Experimental Medicine (I.B., C.A.), Clinical Immunology and Hematology, University of Padova, School of Medicine, Italy; and the Department of Medical and Surgical Sciences (M.M., F.G.), Division of Vascular Surgery, University of Padova, School of Medicine, Italy.
* To whom correspondence should be addressed. E-mail: gianpaolofadini{at}hotmail.com.
Objective--Peripheral arterial disease (PAD) is a threatening complication of diabetes. As endothelial progenitor cells (EPCs) are involved in neovasculogenesis and maintenance of vascular homeostasis, their impairment may have a role in the pathogenesis of diabetic vasculopathy. This study aimed to establish whether number and function of EPCs correlate with PAD severity in type 2 diabetic patients.
Methods and Results--EPCs were defined by the expression of CD34, CD133 and KDR, and quantified by flow cytometry in 127 diabetic patients with and without PAD. PAD severity has been assessed as carotid atherosclerosis and clinical stage of leg atherosclerosis obliterans. Diabetic patients with PAD displayed a significant 53% reduction in circulating EPCs versus non-PAD patients, and EPC levels were negatively correlated with the degree of carotid stenosis and the stage of leg claudication. Moreover, the clonogenic and adhesion capacity of cultured EPCs were significantly lower in diabetic patients with PAD versus patients without.
Conclusions--This study demonstrates that EPC decrease is related to PAD severity and that EPC function is altered in diabetic subjects with PAD, strengthening the pathogenetic role of EPC dysregulation in diabetic vasculopathy. EPC count may be considered a novel biological marker of peripheral atherosclerosis in diabetes.
Key words: stem cells • diabetes • atherosclerosis • endothelium
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