Inter-relationships of indices of endothelial damage/dysfunction [circulating endothelial cells, von Willebrand factor and flow-mediated dilatation] to tissue factor and interleukin-6 in acute coronary syndromes

BACKGROUND: Increased circulating endothelial cells (CECs, reflecting endothelial damage) in acute coronary syndromes (ACS) has been reported. However, the inter-relationships of indices of endothelial damage/injury with development of vascular (dys)function, plasma levels of tissue factor (TF, an index of coagulation) and interleukin-6 (IL-6, a pro-inflammatory cytokine) have not been investigated in ACS. We hypothesized that increased CECs can be related to impaired flow-mediated vasodilatation (FMD, an index of endothelial dysfunction) and elevated plasma von Willebrand factor (vWf, also marking endothelial damage/dysfunction), TF and IL-6 in patients with ACS. METHODS: We studied 120 patients with ACS (80 acute myocardial infarction and 40 unstable angina; 86 male, age 65+/-12 years) and 40 matched patients with stable CAD and 40 healthy controls (HC) in a cross-sectional analysis. Plasma vWf, TF and IL-6 levels were measured by ELISA. CECs were quantified using epifluorescence microscope after immunomagnetic separation with CD146. Brachial artery FMD was assessed in a subset of 39 ACS patients. RESULTS: ACS patients had significantly higher CECs, vWf, TF and IL-6 levels, but lower FMD, when compared to stable CAD and HC (all p<0.001) and all were inter-correlated significantly. In ACS, CECs was strongly correlated with FMD (r=-0.64, p<0.001) and TF (r=0.7, p<0.001). In stable CAD, significant correlations were again found between many indices, but on multivariate analysis, IL-6 and vWf were both independently related to FMD. CONCLUSIONS: Increased CECs in ACS patients are closely associated with endothelial damage/dysfunction (vWf and FMD), coagulation (TF) and inflammation (IL-6). These inter-relationships support the concept of a central role of endothelial damage/injury in the activation of vascular and coagulation abnormalities in ACS.