Circulating endothelial cells

Abstract

Recent research has recognised new populations of non-hematopoietic cells in the blood. One of these, circulating endothelial cells (CECs), often defined by the expression of membrane glycoprotein CD146, are rarely found in the blood in health, but raised numbers are present in a wide variety of human conditions, including inflammatory, immune, infectious, neoplastic and cardiovascular disease, and seem likely to be evidence of profound vascular insult. An additional population are endothelial progenitor cells, defined by the co-expression of endothelial and immaturity cell surface molecules and also by the ability to form colonies in vitro. Although increased numbers of CECs correlate with other markers of vascular disease, questions remain regarding the precise definition, cell biology and origin of CECs. For example, they may be damaged, necrotic or apopototic, or alive, and could possess procoagulant and/or proinflammatory properties. However, since these cells seem to be representative of in situ endothelium, their phenotype may provide useful information. Indeed, whatever their phenotype, there is growing evidence that CECs may well be a novel biomarker, the measurement of which will have utility in various clinical settings related to vascular injury. Despite this promise, progress is impeded by the diversity of methodologies used to detect these cells. Accordingly, results are sometimes inconclusive and even conflicting. Nevertheless, increased CECs predict adverse cardiovascular events in acute coronary syndromes, suggesting they may move from being simply a research index to having a role in the clinic. The objective of the present communication is to condense existing data on CECs, briefly compare them with progenitor cells, and summarise possible mechanism(s) by which they may contribute to vascular pathology.

Involvement of circulating endothelial progenitor cells and vasculogenic factors in the pathogenesis of diabetic retinopathy

“…Furthermore, to prove endothelial lineage of these cells, uptake of acetylated low-density lipoprotein and Ulex Europaeus lectin should be demonstrated. 6 Thus, Lee et al 1 do not positively confirm that the increase in c-Kit þ and CD34 þ cells in their study is due to a concurrent increase in the endothelial progenitor cell fraction, and we suggest that they should be more circumspect in their conclusions.…”

Cells meeting our immunophenotypic criteria of endothelial cells are large platelets

“…This method is based on a single platform whole blood assay without prior cell enrichment, in which CEC are defined as events having low to intermediate forward light scatter (FSC), low sideward light scatter (SSC), and being CD31 þþ , CD45 À , and CD146 þ . Mean CD146 þ CEC counts in healthy donors reported were 7,900 cells per mL by using this approach (8), which is in sharp contrast to numbers observed using enrichment-based methods (typically <100 CEC per mL) (1,10). In view of the large discrepancy between results of single platform methodology and cell enrichment-based methods, we set out to confirm the endothelial nature of FSC low-to-intermedate , SSC low , CD31 þþ , and CD45 À cells in the first approach, which we refer to as ''cells meeting our immunophenotypic criteria of circulating endothelial cells'' (CMOIC).…”

“…Circulating endothelial cells (CEC) are mature endothelial cells shed from injured vasculature (1,2). The concentrations of CEC are reportedly increased in disease conditions associated with vascular damage such as sickle cell anaemia (3), pulmonary hypertension (4), rickettsial infection (5), myocardial infarction (6), ANCA-associated vasculitis (7), and several types of cancer (8).…”

“…Various enumeration methods for CEC have been reviewed by Blann et al (1) and Khan et al (10). Approaches based on cell enrichment (i.e.…”

Flow Cytometry in Preclinical Toxicology/Safety Assessment

“…However, there have since been numerous publications describing correlations between CEC numbers and various human disease states, and CEC enumeration is gaining acceptance as a clinical biomarker of vascular disease [14]. Unfortunately, there is no consensus method for enumeration or immunophenotypic definition of human CEC/CEP [15].…”