P285	Endothelial cell apoptosis, endothelial cell regeneration and the degree of coronary artery disease.
N.Werner, T.Schiegl, P.Ahlers, S.Kosiol, K.Walenta, A.Link, G.Nickenig
Klinik für Innere Medizin III (Kardiologie, Angiologie und Internistische Intensivmedizin), Homburg/Saar, DE.

Background: Endothelial progenitor cells (EPC) contribute to the regeneration of the vascular wall. In order to determine the role of vascular repair in patients with coronary artery disease (CAD) we initiated the large-scale Endothelial Progenitor Cells in Coronary Artery Disease (EPCAD) study. Methods: 519 patients with CAD were prospectively enrolled. FACS analysis of circulating EPC were obtained from all patients to determine the regenerational capacity of each individual. Additional experiments were performed to determine the clonogenic potential of circulating cells. To determine the degree of endothelial cell damage in the patient population, we determined the number of circulating endothelial microparticles (EMP). In order to establish a parameter which resembles the (patho-)physiological situation at the endothelial monolayer, we prospectively defined a vascular repair index (number x function of EPC/ EMP). Results: Arterial hypertension was an independent risk factor associated with increased EMP levels (p<0.001). Age (p=0.021), arterial hypertension (p=0.006) and hypercholesterolemia (p=0.009) were independent predictors for reduced circulating EPC. Age (p<0.001), family history for CAD (p=0.004) and smoking (p=0.028) independently predicted the functional capacity of EPC. The combined evaluation of number and function of EPC together with EMP (vascular repair-index), highly significantly predicted the severity of CAD (p<0.001). In contrast, neither single EPC number and function nor EMP correlated independently with the degree of CAD. Conclusion: EPC significantly correlate with cardiovascular risk factors in patients with CAD. In patients with coronary artery disease, the interaction between endothelial microparticles and vascular progenitor cell number and function predicts the degree of atherosclerotic disease. The vascular repair-index not only provides a novel pathophysiological understanding of atherosclerosis, but may help to non-invasively identify patients with severe coronary artery disease.

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