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Reduced Endothelial Progenitor Cell Number and Function in Inflammatory Bowel Disease

A Possible Link to the Pathogenesis

Garolla, Andrea, MD1; D'Incà, Renata, MD2; Checchin, Davide, MD2; Biagioli, Andrea, MS1; De Toni, Luca, BSc1; Nicoletti, Valentina, BSc1; Scarpa, Marco, MD3; Bolzonello, Elisa, MStat1,4; Sturniolo, Giacomo Carlo, MD2; Foresta, Carlo, MD1

American Journal of Gastroenterology: October 2009 - Volume 104 - Issue 10 - p 2500–2507

OBJECTIVES: Circulating endothelial progenitor cells (EPCs) are essential for endothelial repair and vascular healing. Patients with inflammatory bowel disease (IBD) may suffer from endothelial dysfunction. Reduced EPC number, impaired mobilization, or increased EPC apoptosis may be crucial in this phenomenon. The aim of our study was to investigate the number and function of EPCs in patients with IBD and to assess their endothelial function.

METHODS: In 100 IBD patients (47 ulcerative colitis (UC) and 53 Crohn's disease (CD)) and 50 healthy controls, EPC number, CXC motif receptor 4 (CXCR4) expression, the percentage of apoptotic circulating EPCs, and the number of colony-forming units were evaluated. Endothelial dysfunction was assessed by luteinizing hormone (LH), follicle stimulating hormone (FSH), and testosterone levels, and in a subgroup of patients, brachial artery flow-mediated dilation (FMD) was measured. Kruskal-Wallis ANOVA (analysis of variance), Mann-WhitneyUtwo-tailed, and Spearman's rank correlation tests were used to assess differences.

RESULTS: EPC number was significantly lower in UC patients (39.6 (95% confidence interval (95% CI): 30.7-48.6)) and in CD patients (43.1 (95% CI: 35.9-50.4)) than in healthy controls (97.1 (95% CI: 88.3-105.9)), (P<0.001). LH and FSH levels and CXCR4 expression on EPCs did not significantly differ from controls. Testosterone concentrations and FMD were lower in UC patients. Number of apoptotic EPCs was higher in both UC and CD patients with an impaired ability to generate colonyin vitro.

CONCLUSIONS: We hypothesize that in IBD patients, apoptosis contributes to the reduction of circulating EPC number and to their ability to proliferatein vitro.As this condition represents a risk factor for cardiovascular disease, endothelial function should be evaluated in these patients.

Am J Gastroenterol 2009; 104:2500-2507; doi:10.1038/ajg.2009.332; published online 30 June 2009

1Department of Histology, Microbiology, and Medical Biotechnologies, Center for Male Gamete Cryopreservation, University of Padova, Padova, Italy; 2Department of Surgical and Gastroenterological Sciences, Section of Gastroenterology, University of Padova, Padova, Italy; 3Department of Surgery, Veneto Oncological Institute, Padova, Italy; 4Sinodè, Padova, Italy. Correspondence: Carlo Foresta, MD, Center for Male Gamete Cryopreservation, University of Padova, Via Gabelli 63-35128, Padova, Italy. E-mail:

Received 12 February 2009; accepted 4 May 2009

© The American College of Gastroenterology 2009. All Rights Reserved.
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