Circulating Endothelial Cells: Markers and Mediators of Vascular Damage

Uta      Erdbruegger; Ajay      Dhaygude; Marion      Haubitz; Alexander      Woywodt

Abstract

About 30 years ago circulating endothelial cells (CEC) were first observed in peripheral blood. Since then CEC have been established as a reliable indicator of vascular injury and damage and more sophisticated detection techniques, such as immunomagnetic isolation and fluorescence-activated cell sorting (FACS), have become available. However even today there remains controversy as to the best approach to isolate and enumerate these cells. Here, we review the isolation and enumeration of CEC with an emphasis on CD146- driven immunomagnetic isolation and FACS as the two competing techniques. We describe advantages and pitfalls of both approaches. Moreover, we provide a list of clinical studies in this field and describe the possible clinical utility of CEC as a surrogate marker for vascular damage and dysfunction. In addition, we review the phenotype of CEC and discuss mechanisms of detachment. Recent evidence has also revealed interesting interactions between CEC and healthy endothelium in vitro although the relevance of these findings for human vascular disease in vivo remains unclear. Finally, we highlight differences between circulating endothelial cells and endothelial progenitor cells. In summary, CEC must be regarded as a sensitive and specific marker of endothelial damage as well as a potential mediator in vascular disease.

Keywords: Circulating endothelial cells, vascular damage, blood markers, light microscopy, mature, smoking, acute myocardial infarction, hypertension, morphological, Immuno-fluorescence, techniques for isolation, enumeration, IMMUNOMAGNETIC ISOLATION, paramagnetic particles, traumatic, venepuncture, Fc-blocking agents, T-lymphocytes, trophoblast, mesenchymal stem cells, Ulex Europaeus lectin, multinucleated cell, phenotype, FLUORESCENCE, co-staining, propidium iodide, intercellular adhesion molecule-1, E-selectin, pro-coagulant activity, platelets, validation studies, VASCULAR DISORDERS, endothelial lesion, rickettsial infection, sickle cell disease, coronary angioplasty, acute myocardial infarction, atrial fibrillation, arterial stiffness, risk of cardiovascular death, necrotic phenotype, granulomatous disease, Kawasaki's syndrome, lupus erythematosus, cytomegalovirus, Transplantation, kidney transplantation, calcineurine inhibitors, donor origin, bone marrow cell transplantation, Thrombotic microangiopathy, plasma exchange, hematological disease, chronic myelo-proliferative disease, breast cancer, lymphoma patients, bronchogenic carcinoma, tumor necrosis, DETACHMENT OF ENDOTHELIAL CELLS, oxidative stress, apoptotic, necrotic cells, cytomegalovirus infection, endothelial progenitor cells, adhesive properties of the endothelial cells, Viral infections, membrane proteins, Potential Mediators of Disease, pro-inflammatory, eukaryotic cells, monocytes, fibroblasts, phagocytic, chemo-attractants, thrombospondin, multi-functional glycoprotein, acetylated low-density lipoprotein, hematopoietic stem cells, inability to growth