Regular Article HDL cholesterol is a strong determinant of endothelial progenitor cells in hypercholesterolemic subjects Fabio Rossi, Cora Bertone, Federica Montanile, Federica Miglietta, Carla Lubrano, Loredana Gandini, Vittorio Santiemma ⁎ Dipartimento di Fisiopatologia Medica, Sapienza Università, Rome, Italy abstract article info Article history: Received 22 January 2010 Revised 5 May 2010 Accepted 6 May 2010 Available online 15 May 2010 Keywords: EPC Hypercholesterolemia HDL-C LDL-C Endothelial Function Gender Cardiovascular risk factor Endothelium-dependent vasodilatation Plethysmography Endothelial progenitor cells (EPC) can repair the endothelial layer and are considered a component of the cardiovascular system. EPC number and function may change under pathological conditions, including cardiovascular risk factors. The study was carried out to investigate circulating EPC number, in vitro function and relationship with LDL-C, HDL-C and endothelium-dependent vasodilatation in hypercholesterolemic subjects. Forty-one male and 39 female subjects, age N35 and b45, LDL cholesterol plasma level N 130 mg/dl with normal (≥50 mg/dl females and ≥ 40 mg/dl males) or low HDL-C, absence of any concomitant disorders and/or drug treatment, at their first diagnosis of hypercholesterolemia, were consecutively recruited in the Outpatient Service of the Medical Pathophysiology Department of Rome Sapienza University. In high LDL-C patients, circulating EPC number was decreased and EPC capability to migrate was impaired as well. This pattern was far less evident in the normal HDL-C subgroup. The endothelium-dependent vasodilatation (EDV) was significantly decreased according to the HDL-C decrease in male but not in female subjects. Univariate analysis showed a direct correlation between EPC number and EDV, and the association persisted after adjustment for sex, age and HDL-C, which were all significantly correlated to EDV, which may suggest a protective role of EPC on endothelium in vivo. Our study documented that, in hypercholesterolemic subjects, HDL-C is a strong determinant of EPC number and function, and EPC number decrease is an independent risk factor for endothelial dysfunction. © 2010 Elsevier Inc. All rights reserved. Introduction Endothelial progenitor cells (EPC), a subtype of immature cells involved in angiogenesis, constitute a pool of cells identifiable among circulating peripheral mononucleate cells (Asahara et al., 1997), that can actively repair the endothelial layer by forming a patch at sites of intimal damage (Werner et al., 2002; Kong et al., 2004). Circulating EPC can be mobilized from the bone marrow by numerous stimuli able to induce the release of growth factors (Werner et al., 2002; Kong et al., 2004). Thanks to their comprehen- sive role in endothelial regeneration and compensatory angiogenesis, EPC are currently considered an integrated component of the cardiovascular system that is subject of intense research and debate (Urbich and Dimmeler, 2004). Not only normal EPC number but also normal EPC function is required for adequate homeostasis (Fadini et al., 2007). EPC number as well as their proliferative potential may change under pathological conditions, including cardiovascular risk factors such as genetic predisposition or smoking (Vasa et al., 2001), coronary artery disease (Adams et al., 2004), diabetes mellitus, and rheumatoid arthritis (Grisar et al., 2005; Herbrig et al., 2006; Tepper et al., 2002). Also some drugs and growth factors, such as HMG-CoA reductase inhibitors (Dimmeler et al., 2001), G-CSF (Peichev et al., 2000) and erythropoietin (Bahlmann et al., 2004) affect EPC number. Altered lipid plasma level is associated to coronary artery disease (CAD), stroke and peripheral vascular disease. Increased low density lipoprotein cholesterol (LDL-C) is acknowledged to be an independent cardiovascular (CV) risk factor, and treatment aimed to reduce LDL-C plasma level is associated to decreased incidence of CAD and stroke (Baigent et al., 2005; Wilensky and Macphee, 2009; Amarenco and Labreuche, 2009). It has been suggested that LDL-C may not be the best indicator for the presence of coronary artery disease (Walldius and Jungner, 2004) and it is well-known that plasma HDL-C levels are inversely correlated with the risk of cardiovascular disease, as was first demonstrated by the Framingham study (Gordon et al., 1977). Interestingly, no correlation was demonstrated between EPC number or function and LDL-C plasma levels in subjects with risk factors for coronary artery disease (Vasa et al., 2001). Conversely, impairment of Microvascular Research 80 (2010) 274–279 ⁎ Corresponding author. Dipartimento di Fisiopatologia Medica, V Clinica Medica Policlinico Umberto I Sapienza Università di Roma, Viale del Policlinico, 00161 Rome, Italy. Fax: +39 06 490530. E-mail address: vittorio.santiemma@uniroma1.it (V. Santiemma). 0026-2862/$ – see front matter © 2010 Elsevier Inc. All rights reserved. doi:10.1016/j.mvr.2010.05.003 Contents lists available at ScienceDirect Microvascular Research journal homepage: www.elsevier.com/locate/ymvre