Are impaired endothelial progenitor cells involved in the processes of late in-stent thrombosis and re-endothelialization of drug-eluting stents?
Drug-eluting stent (DES) now is the default selection for most of the interventional cardiologists. However, its benefits compromised by the stent-related thrombosis events. Given the catastrophic consequences, it is important to investigate possible mechanisms of stent thrombosis. The cause of stent thrombosis is multifactorial, and several stent-related and patient-related variables have been identified. The stent itself has components that may lead to thrombosis: the metal stent material, the polymer which houses the drug, and the actual cell-cycle inhibiting drugs. Most important the cell-cycle inhibitors (sirolimus and paclitaxel) reduce neointimal formation by impeding smooth muscle cells proliferation and migration, these drugs also impair the normal process of the injured arterial wall and cause delayed re-endothelialization [Tsimikas S. Drug-eluting stents and late adverse clinical outcomes. J Am Coll Cardiol 2006;47:2112-5; Colombo A, Drzewiecki J, Banning A, et al. Randomized study to assess the effectiveness of slow- and moderate-release polymer-based paclitaxel-eluting stent for coronary artery lesions. Circulation 2003;108:788-94; Kedia Gautam, Lee Michael S. Stent thrombosis with drug-eluting stents: a re-examination of the evidence. Catheter Cardiovasc Interv 2007;69:782-9] [1-3]. It has been proposed that bone marrow-derived endothelial progenitor cells may also be involved in re-endothelialization [Urao N, Okigaki M, Yamada H, et al. Erythropoietin-mobilized endothelial progenitors enhance reendothelialization via Akt-endothelial nitric oxide synthase activation and prevent neointimal hyperplasia. Circ Res 2006;98:1405-13; Griese DP, Ehsan A, Melo LG, et al. Isolation and transplantation of autologous circulating endothelial cells into denuded vessels and prosthetic grafts: implications for cell-based vascular therapy. Circulation 2003;108:2710-15] [4-5]. Interestingly, rapamycin inhibits proliferation, migration, and differentiation of human endothelial progenitor cells in vitro [Butzal M, Loges S, Schweizer M, et al. Rapamycin inhibits proliferation and differentiation of human endothelial progenitor cells in vitro. Exp Cell Res 2004;300:65-71; Chen TG, Chen JZ, Wang XX. Effects of rapamycin on number activity and eNOS of endothelial progenitor cells from peripheral blood. Cell Proliferat 2006;39:117-25]. We hypothesis that drugs loaded on DES may affect the number as well as the homing and proliferation of endothelial progenitor cells, thus further preventing proper endothelial healing, increasing platelet aggregation, which could lead to stent thrombosis.
Zhao
Fu Hai
FH
Ward 1st, Department of Cardiology, Beijing AnZhen Hospital Affiliated to Capital University of Medical Sciences, Chaoyang District, Beijing 100029, PR China.
Chen
Yun Dai
YD
Jin
Ze Ning
ZN
Lu
Shu Zheng
SZ
D002455:Cell Division / Q000187:drug effects; D002465:Cell Movement / Q000187:drug effects; D023903:Coronary Restenosis / Q000517:prevention & control; D054855:Drug-Eluting Stents; D004730:Endothelium, Vascular / Q000187:drug effects / Q000502:physiology*; D015672:Erythroid Precursor Cells / Q000473:pathology*; D006801:Humans; D017239:Paclitaxel / Q000627:therapeutic use; D020123:Sirolimus / Q000627:therapeutic use; D015607:Stents / Q000009:adverse effects*; D013927:Thrombosis / Q000209:etiology* / Q000473:pathology; D017211:Treatment Failure
D017239:Paclitaxel; D020123:Sirolimus