European Heart Journal Advance Access originally published online on February 13, 2007
European Heart Journal 2007 28(5):639-640; doi:10.1093/eurheartj/ehl519
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Endothelial progenitor cells and erectile dysfunction
Department of Clinical and Experimental Medicine
University of Padova Medical School
Via Giustiniani 2
Padova 35100
Italy
Department of Clinical and Experimental Medicine
University of Padova Medical School
Padova
Italy
Department of Clinical and Experimental Medicine
University of Padova Medical School
Padova
Italy
Tel: +39 049 8212185 Fax: +39 049 8212184 E-mail address: gianpaolofadini{at}hotmail.com
Baumhäkel and coworkers have recently examined the levels of circulating CD34+KDR+ and CD133+ cells in patients with coronary artery disease (CAD), which were evaluated for the presence of erectile dysfunction (ED). They show that CD133+, but not CD34+KDR+, cell count negatively correlates with ED score and is independently associated with ED. Although this is an intriguing observation linking ED and CAD with depletion of progenitor cells, there are methodological issues that limit interpretation of this study.
In describing flow cytometry, the authors have not indicated the antibodies used and have not specified whether direct or indirect staining was performed. Moreover, the number of events acquired for the analyses is far too low for a reliable enumeration of rare events, such as progenitor cell count.1 It is not clear why CD133+ cells were not studied for co-expression of CD34+ and KDR+. In fact, CD133 is a marker of immature haematopoietic stem cells,2 although, by definition, identification of endothelial progenitor cells (EPCs) relies on the co-expression of at least one endothelial marker, such as KDR.3 Additionally, CD133+KDR+ cells constitute a small fraction of the total EPC pool,4 and the count of CD133+ generic progenitors is poorly correlated with levels of CD34+KDR+ or CD133+KDR+ or CD34+CD133+KDR+ EPC.5 Therefore, EPC cannot be defined by the sole expression of CD133, because most undifferentiated circulating CD133+ cells are haematopoietic in nature.
It was strange that CD34+KDR+ cells, which is to date the most widely accepted EPC phenotype,6 did not correlate with ED. To explain this contradictory result, the authors refer to a paper in which they show that endothelial cells are more vasculogenic when differentiated in vitro from CD34–CD133+ than from CD34+CD133+ cells; yet, they suggest that CD34–CD133+ cells are precursors of CD34+CD133+ cells.7 Clearly, those experiments cannot be directly translated to the ex vivo determination of circulating EPC with flow cytometry. Rather, we suggest that, as CD34+KDR+ EPC should be profoundly reduced in CAD patients, a 10 000-event analysis has a too low sensitivity to reveal further differences of double-positive cells in ED patients.
In conclusion, there is a compelling need for a consensus on EPC definition and methods for their evaluation.
References
- Khan SS, Solomon MA, McCoy JP Jr. (2005) Detection of circulating endothelial cells and endothelial progenitor cells by flow cytometry. Cytometry B Clin Cytom 64:1–8.[Medline]
- Wognum AW, Eaves AC, Thomas TE. (2003) Identification and isolation of hematopoietic stem cells. Arch Med Res 34:461–475.[CrossRef][ISI][Medline]
- Urbich C and Dimmeler S. (2004) Endothelial progenitor cells: characterization and role in vascular biology. Circ Res 95:343–353.
[Abstract/Free Full Text] - Fadini GP, Sartore S, Albiero M, Baesso I, Murphy E, Menegolo M, Grego F, Vigili de Kreutzenberg S, Tiengo A, Agostini C, Avogaro A. (2006) Number and function of endothelial progenitor cells as a marker of severity for diabetic vasculopathy. Arterioscler Thromb Vasc Biol 26:2140–2146.
[Abstract/Free Full Text] - Fadini GP, de Kreutzenberg SV, Coracina A, Baesso I, Agostini C, Tiengo A, Avogaro A. (2006) Circulating CD34+ cells, metabolic syndrome, and cardiovascular risk. Eur Heart J 27:2247–2255.
[Abstract/Free Full Text] - Fadini GP, Coracina A, Baesso I, Agostini C, Tiengo A, Avogaro A, Vigili de Kreutzenberg S. (2006) Peripheral blood CD34 + KDR + endothelial progenitor cells are determinants of subclinical atherosclerosis in a middle-aged general population. Stroke 37:2277–2282.
[Abstract/Free Full Text] - Friedrich EB, Walenta K, Scharlau J, Nickenig G, Werner N. (2006) A CD34–/CD133+/VEGFR-2+ endothelial progenitor cell subpopulation with potent vasoregenerative capacities. Circ Res 98:e20–25.
[Abstract/Free Full Text]
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