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J Am Coll Cardiol, 2005; 45:1449-1457, doi:10.1016/j.jacc.2004.11.067 © 2005 by the American College of Cardiology Foundation |
* Department of Clinical and Experimental Medicine, Division of Metabolic Diseases, University of Padova, School of Medicine, Padova, Italy
Department of Clinical and Experimental Medicine, Clinical Immunology and Hematology, University of Padova, School of Medicine, Padova, Italy
Department of Medical and Surgical Sciences, Division of Vascular Surgery, University of Padova, School of Medicine, Padova, Italy
Manuscript received August 20, 2004; revised manuscript received November 8, 2004, accepted November 22, 2004.
* Reprint requests and correspondence: Dr. Gian Paolo Fadini, Department of Clinical and Experimental Medicine, University of Padova, School of Medicine, Via Giustiniani 2, 35128 Padova, Italy (Email: angelo.avogaro{at}unipd.it).
OBJECTIVES: We sought to establish whether a reduction in endothelial progenitor cells (EPCs) has a putative role in peripheral vascular disease (PVD) of type 2 diabetic patients.
BACKGROUND: Peripheral vascular disease is a common and severe complication of diabetes mellitus. Impaired collateralization of diabetic vasculopathy has been extensively shown, but causes leading to its pathogenesis are not fully understood. Recently, EPCs have been found to contribute to vascular repair and angiogenesis. Diabetes has been associated with low levels of circulating EPCs, but no data are available in the literature on the relationship between EPCs and PVD in diabetes.
METHODS: Flow cytometric analysis was used to quantify circulating progenitor cells (CPCs, CD34+) and EPCs (CD34+KDR+) in 51 patients and 17 control subjects.
RESULTS: The CPCs and EPCs from diabetic patients were reduced by 33% and 40%, respectively, compared with healthy subjects (p < 0.001). An inverse correlation was found between the number of EPCs and the values of fasting glucose (r = –0.49, p = 0.006). Peripheral vascular disease was associated with a 47% reduction in EPCs (p < 0.0001) and EPC levels directly correlated with the ankle-brachial index (r = 0.70, p = 0.01). The subgroup of diabetic patients with PVD also had reduced CPCs by 32% (p = 0.037), whereas patients with ischemic foot lesions had the lowest levels of both EPCs and CPCs (p = 0.02).
CONCLUSIONS: Our data demonstrate decreased EPC levels in diabetic patients and, for the first time, show that PVD is associated with an extensively low number of EPCs. Depletion of circulating EPCs in diabetic patients may be involved in the pathogenesis of peripheral vascular complications.
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