Abstract 12206: Mobilization of Bone Marrow-Derived Endothelial Progenitor Cells and Re-Endothelialization After Coronary Stent Implantation -Assessment in Second Generation Drug Eluting Stents-
Although drug-eluting stent (DES) technology has demonstrated reduced restenosis, a new concern is that DESs may impair re-endothelialization, which is essential for the wound healing process in the injured vessel wall. Regenerative endothelial cells in re-endothelialization have been considered, in part, derived from bone marrow-derived endothelial progenitor cells (EPCs). We previously demonstrated that circulating bone marrow-derived CD34+ stem cells increased 7-14 days after bare metal stent (BMS) implantation, leading to restenosis. However, the sirolimus eluting stent (SES) substantially suppressed increases in circulating CD34+ cells. In the present study, we assessed the mobilization of EPCs and the wound healing response in the second generation DESs, zotarolimus-eluting stent (ZES) and everolimus-eluting stent (EES). In 38 patients receiving coronary stent implantation (70±9 yrs; BMS, n=15; ZES, n=9; EES, n=14), we measured circulating CD34+/CD133+/CD45low EPCs at baseline and 7 days after stenting. In 17 patients, at a late time point (average 10 months), we observed neointimal coverage for all stents using optical coherence tomography (OCT) imaging and calculated the uncovered ratio. In addition, we cultured isolated circulating mononuclear cells obtained from 5 healthy volunteers to observe their differentiation into vascular cells and compared the effects of sirolimus, zotarolimus and everolimus. The number of circulating EPCs on day 7 after coronary stent implantation showed increases of 74±59%, 13±55% (P≤0.05 vs BMS), and 1±40% (P≤0.001 vs BMS) in the BMS, ZES and EES groups, respectively. The uncovered ratio was 2.4±4.0%, 2.6±1.9%, and 41.6±25.6% (P≤0.001 vs BMS) in the BMS, ZES and EES groups, respectively. The uncovered ratio and the percent increase in EPC showed a negative correlation (R=-0.42, P≤0.05). The differentiation of mononuclear cells into endothelial-like cells was dose-dependently inhibited by sirolimus, zotarolimus, and everolimus with the strongest inhibition by sirolimus. These results suggest that mobilization of EPCs might lead to re-endothelialization and that even second generation DESs remain problematic in terms of the wound healing process after vascular injury.
- © 2013 by American Heart Association, Inc.