Number and Adhesive Properties of Circulating Endothelial Progenitor Cells in Patients With In-Stent Restenosis

OBJECTIVE: Intact endothelialization machinery is essential to facilitate vessel healing after stent placement and to prevent restenosis. Circulating endothelial progenitor cells (EPC) have been demonstrated in the peripheral blood and shown to display endothelial functional properties, along with the ability to traffic to damaged vasculature. We reasoned that robust in-stent intimal growth could be partially related to impaired endothelialization resulting from reduced circulating EPC number or function. METHODS AND RESULTS: Sixteen patients with angiographically-demonstrated in-stent restenosis were compared with patients with a similar clinical presentation that exhibited patent stents (n=11). Groups were similar with respect to the use of drugs that could potentially influence EPC numbers. Circulating EPC numbers were determined by the colony-forming unit assay, and their phenotype was characterized by endothelial-cell markers. Adhesiveness of EPC from both groups to extracellular matrix and to endothelial cells was also assayed. Patients with in-stent restenosis and with patent stents displayed a similar number of circulating EPC. Fibronectin-binding was compromised in patients with in-stent restenosis as compared with their controls exhibiting patent stents. Patients with diffuse in-stent restenosis exhibited reduced numbers of EPC in comparison with subjects with focal in-stent lesions. CONCLUSIONS: Reduced numbers of circulating EPC in patients with diffuse in-stent restenosis and impaired adhesion of EPC from patients with restenosis provides a potential mechanism mediating the exuberant proliferative process. These markers, if further validated, could provide means of risk stratifying patients for likelihood of developing in-stent restenosis.