articleSmoking decreases the level of circulating CD 34 + progenitor cells in young healthy women-a pilot study

Background: Decreased levels of circulating bone marrow-derived progenitor cells have been associated with risk factors and cardiovascular diseases. Smoking is the most important modifiable risk factor for atherosclerosis in young women. The aim of this pilot study was to assess in healthy premenopausal women without other risk factors for cardiovascular disease the influence of nicotine abuse on the number of circulating progenitor cells in relation to endothelial function. Methods: The number of endothelial progenitor cells, measured as colony-forming units in a cell-culture assay (EPCCFU) and the number of circulating CD34 + and CD34 + /CD133 + cells, measured by flow cytometry, was estimated in 32 women at the menstrual phase of the menstrual cycle. In addition, flow-mediated dilation (FMD) was assessed as a marker for vascular function. In a subgroup of these women (n = 20), progenitor cells were also investigated at the midfollicular and luteal phases of the menstrual cycle. Results: Compared to non-smokers, the abundance of circulating CD34 + cells was significantly lower in smoking women in the menstrual, mid-luteal, and mid-follicular phases of the menstrual cycle. The number of CD34 + progenitor cells was revealed to have significant positive correlation with FMD in young healthy women, whereas CD34 + /CD133 + progenitor cells and EPC-CFU showed no significant correlation. Conclusion: The number of CD34 + progenitor cells positively correlates with FMD in young healthy women and is decreased by smoking. Background Vascular homeostasis is controlled not solely by cells of the vessel wall, but also by circulating bone marrowderived progenitor cells (PCs). In particular, a subset of circulating stem cells, designated endothelial progenitor cells (EPCs), is considered to contribute to endothelial cell regeneration and neovascularisation [1]. Levels of circulating PCs/EPCs have been correlated with endothelial function, atherogenic risk factors, as well as various cardiovascular diseases [2-5]. Although prospective data are still lacking, the number of PCs/EPCs is evidently inversely related to cardiovascular risk [6,7]. Since a clear and generally accepted definition of EPCs has until now not been established, most studies investigating the nature and function of EPCs have focused on flow-cytometric analysis of circulating cells that are positive for the haematopoietic stem cell markers CD34, CD133 and for the vascular endothelial growth factor receptor 2 (VEGFR2), and/or have concentrated on analysis of in vitro formation of colony-forming units (EPCCFU) [1,6]. There is some evidence that levels of circulating progenitor cells positive for CD34 (CD34 + cells) are more strongly correlated with cardiovascular risk factors than are progenitor cell populations with various combinations of CD34, CD133, and VEGFR2 [6]. Women of reproductive age are exposed to lower cardiovascular risk than are age-matched men [8]. This is generally attributed to differences in sex hormones and, * Correspondence: verena.stangl@charite.de 1 Med. Klinik mit Schwerpunkt Kardiologie und Angiologie, Charité Universitaetsmedizin Berlin, Campus Mitte, Berlin, Germany † Contributed equally Full list of author information is available at the end of the article © 2010 Ludwig et al; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Ludwig et al. BMC Women's Health 2010, 10:20 http://www.biomedcentral. com/1472-6874/10/20 Page 2 of 8 specifically, to the protective cardiovascular properties of female estrogens [9,10]. Notably, elevated estrogen plasma concentrations in women correlate with higher levels of circulating EPCs [11]. They accordingly promote vascular repair and inhibit neointima formation after carotid artery injury in mice [11]. The effects of estrogens on EPCs are mediated by nitric oxide and antiapoptotic mechanisms [11,12]. Changes in hormonal levels during the menstrual cycle are likewise reflected in the number of circulating progenitor cells. The highest levels of progenitor cells positive for CD34 and CD133 (CD34 + / CD133 +) were measured following the pre-ovulatory phase: i.e., the cycle phase with the highest levels of estrogens [13-15]. Smoking is the most important modifiable risk factor for atherosclerosis in young women [16]. The biological mechanisms linking smoking and atherogenesis are complex and not fully understood. In addition to inflammation, potential mechanisms by which smoking increases the risk of cardiovascular diseases include systemic haemostatic and coagulatory disturbances, lipid abnormalities, increase in oxidative stress, and vascular endothelial dysfunction [17-19]. It has been shown that smoking attenuates the number of progenitor cells in the circulatory system of male individuals, and that smoking cessation leads to a rapid elevation in progenitor cell levels [20]. It is presently unknown whether there is a link between smoking and the amount of progenitor cells in women in which endogenously released estrogens may further influence progenitor cell levels. The aim of the present study was accordingly to investigate whether smoking influences the number of progenitor cells in young healthy women without other cardiovascular risk factors, and whether there is correlation between the amount of progenitor cells and endothelial function assessed as flow-mediated dilation (FMD) of the brachial artery.