Werner et al

Werner et al. diseases. This trial is registered with DM4 registration number: ProsperoCRD42015023717. == 1 . Intro == Endothelial progenitors cells (EPCs) are a heterogeneous population of cells in different says of maturation, originated from bone marrow (BM). Since their identification by Asahara et al. [1], a great effort has been directed to explore the regenerative/reparative potential of EPCs, such as the capability of self-renewal, of starting reparative mechanisms, and of neoangiogenesis [24]. However , EPC isolation and characterization are still debated; in literature, two different approaches have been used to evaluate EPCs: identification of subpopulations based on surface markers from fresh blood and culture/colony assays. The methods intended for isolating circulating cells include adherence culture of total mononuclear cells obtained from fresh blood by density gradient centrifugation, positive preselection of mononuclear cells by antibodies against surface marker, and finally acquisition and analysis by flow cytometry [1, 5, 6]. Different culture methods were made by different working groups, which differ between them intended for the time of growth, intended for the press used, DM4 and for cell phenotypes. The common methods used may be summarized as EPC culture assay [7, 8], colony-forming unit-endothelial cell (CFU-EC) colony assay [9], and endothelial colony-forming cells (ECFC) [1012]. Moreover, there is no clear evidence as to the existence of such culture-derived cells in vivo, and, more importantly, the relevance of such cells has not been functionally demonstrated in the clinical context [13, 14]. Many different surface antigens, often coexpressed by endothelial and hematopoietic cells, have been proposed and used to identify putative EPCs, including CD34, CD117, CD133, CD105, CD144, CD184, CD309 (KDR or VEGFR2), acetylated low-density lipoprotein, and various plant lectins [15], so the question of which cell phenotype better identifies the true circulating EPC remains unsolved; the more widely studied progenitor phenotypes, also despite some evidence in clinical studies, do not give rise to mature endothelial cells in cultures and are different from endothelial colony-forming cells [12, 16, 17], although the ability to differentiate in vivo into a broad range of cell types of different organs and systems, including cardiomyocytes, smooth muscle cells, and endothelial progenitor cells (EPCs), as well as hematopoietic, stromal, and epithelial cells, has been suggested, with a role in cooperating with EPCs for postnatal vasculogenesis, working as proangiogenic support cells, participating in the turnover of healthy and damaged endothelium, maintaining their importance as regenerative/reparative potential, and also as prognostic markers [1522], likely delaying the development of atherosclerosis and cardiovascular disease (CVD). Moreover, it has been suggested that different circulating progenitors show an important differentiation and also transdifferentiation ability [2224]. Over the last 15 years, many studies focused on the role of EPCs in clinical conditions characterized by increased cardiovascular KAT3B (CV) risk, such as smoke publicity, hypertension, diabetes, dyslipidemia, and aging, and in general by atherosclerotic DM4 disease (coronary artery disease DM4 (CAD), acute myocardial infarction (AMI), cerebrovascular disease, and stroke). This literature review aims to give an overview on the current stand of knowledge on the so-called EPCs, including insights into their use intended for diagnosis DM4 and prognosis of CVD. == 2 . Methods == This review was performed following methods that are reported in the PRISMA Statement. A systematic literature search was conducted in PubMed MEDLINE from January 2000 to December 2014. MEDLINE was searched using keywords related to endothelial progenitor cells and endothelium and, for the different categories, respectively, smoking; blood pressure; diabetes mellitus or insulin resistance; dyslipidemia; aging or elderly; angina pectoris or myocardial infarction; stroke or cerebrovascular disease; homocysteine; C-reactive protein; vitamin D. We recognized 299 out of 927 publications, so divided: 32 out of 47 intended for smoking; 21 out 78 for blood pressure; 63 out of 137.