Markers of Vascular Damage and Repair

Damage to endothelial cells is a crucial event during the pathogenesis of vasculitis. The vasculitides cause different clinical manifestations, depending on the extent and acuity of endothelial damage as well as their preponderance to affect some organ-specific endothelial cells and spare others. About 40 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 to detect and enumerate them. Based on current concepts of pathogenesis, detached endothelial cells, and/or their soluble and cellular debris, must be detectable in peripheral blood of vasculitis patients. In hindsight, it is therefore surprising that for many years few, if any, attempts were made to evaluate their use as clinically relevant markers of endothelial damage. Endothelial Microparticles (eMP) have been described as another potential marker of endothelial damage. eMP are markers of activation, cell injury or apoptosis. They are the product of exocytic budding and consist of cytoplasmic components and phospholipids. Fluorescence-activated cell sorting (FACS) is the preferred technology for isolating MP and different surface markers of the parent cells have been used. eMP can reflect endothelial activation and damage, although differences between eMP and CEC remain ill-defined. Another approach to measuring endothelial damage is to assay soluble markers, such as thrombomodulin or von Willebrand factor. However, these markers also have their limitations. It is also worthwhile to remember that all approaches struggle with the fact that many endothelial markers are also expressed on non-endothelial cells (Table 1). More recently, interest has focused on endothelial repair and damage and endothelial progenitor cells have been studied, again with different methodologies. 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. Here, we review markers of endothelial damage and repair in vasculitis. We discuss the implications of these findings for the pathogenesis, their potential clinical utility, and also review the limitations of each approach. Finally, we review the phenotype of CEC, mechanisms of detachment and interactions with other cell subsets.