Assessment of endothelial damage in atherosclerotic vascular disease by quantification of circulating endothelial cells. Relationship with von Willebrand factor and tissue factor.

Abstract

Increased numbers of CD146-defined circulating endothelial cells (CECs), as are present in the peripheral blood of patients suffering acute coronary syndromes, imply injury to the endothelium. Endothelial damage can also be assessed by the measurement of plasma levels of von Willebrand factor (vWf). Increased levels of procoagulant plasma tissue factor (TF), arising from monocytes/macrophages and endothelial cells, is present in atherosclerosis. We hypothesised increased CECs in patients with ischaemic rest pain (IRP) of the lower limb due to peripheral atherosclerosis and comparable to that seen in patients with acute myocardial infarction (AMI), when compared to patients with intermittent claudication (IC) or healthy controls that would correlate with vWf and TF. We recruited 20 patients in each of four groups: (i) IRP of the lower limb; (ii) AMI; (iii) 'stable' IC; and (iv) healthy controls. CD146-expressing CECs were measured by immumomagnetic separation and counting under a fluorescence microscope; plasma vWf and TF by ELISA. In IRP, median (IQR) CEC levels were 3.5 (2.0-5.8) cells/ml, in IC were 1.1 (0.6-2.9) cells/ml, and in healthy controls were 1.0 (0.5-1.7) cells/ml (p<0.001). The levels of vWf (p=0.034) and TF (p=0.007) were also significantly different between the groups, with the highest levels in patients with IRP. Levels of CECs correlated with vWf (rs=0.4, p=0.002) and TF ( rs=0.296, p=0.021 ). In AMI, CEC levels were higher than those in IRP at 4.9 (3.6-8.4) cells/ml (p=0.0385). This study demonstrates evidence of direct endothelial cell injury (i.e. raised CECs) in patients with IRP that correlated with vWf and TF, but that this is less severe than in AMI.