Drug-eluting stents: sirolimus and paclitaxel differentially affect cultured cells and injured arteries.
Sirolimus and paclitaxel eluted from stents inhibit cell proliferation and other cellular processes by dramatically different mechanisms. In this study, the effects of sirolimus and paclitaxel on cultured human coronary artery smooth muscle and endothelial cell function or cell cycle changes in balloon-injured arteries were directly compared. Both sirolimus and paclitaxel inhibited smooth muscle and endothelial cell proliferation. However, only paclitaxel inhibited smooth muscle and endothelial cell migration at low (nM) concentrations. Sirolimus arrested smooth muscle and endothelial cells in the G0/G1 phase of the cell cycle without inducing apoptosis while paclitaxel produced apoptosis in both cell types at low nanomolar concentrations. Although both agents blocked neointimal formation, sirolimus applied locally to injured rat carotid arteries increased the percentage of cycling vascular cells in G0/G1 without inducing apoptosis while paclitaxel increased the percentage of cycling cells in S and G2/M phases while inducing apoptosis. These results suggest that sirolimus reduces neointimal hyperplasia through a cytostatic mechanism while paclitaxel produces apoptotic cell death.
Parry
Tom J
TJ
Cordis Corporation, a Johnson and Johnson Company, Warren, NJ, USA.
Brosius
Ruth
R
Thyagarajan
Rathna
R
Carter
Demetrius
D
Argentieri
Dennis
D
Falotico
Robert
R
Siekierka
John
J
D000818:Animals; D000903:Antibiotics, Antineoplastic / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects; D020212:Carotid Artery Injuries / Q000150:complications / Q000473:pathology / Q000517:prevention & control*; D002453:Cell Cycle / Q000187:drug effects; D002465:Cell Movement / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects*; D002470:Cell Survival; D002478:Cells, Cultured; D003331:Coronary Vessels / Q000166:cytology / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D016503:Drug Delivery Systems; D042783:Endothelial Cells / Q000166:cytology / Q000187:drug effects; D006965:Hyperplasia / Q000209:etiology; D008297:Male; D009131:Muscle, Smooth, Vascular / Q000166:cytology / Q000187:drug effects; D017239:Paclitaxel / Q000494:pharmacology*; D051381:Rats; D011917:Rats, Inbred Lew; D020123:Sirolimus / Q000494:pharmacology*; D015607:Stents; D017539:Tunica Intima / Q000187:drug effects / Q000473:pathology
D000903:Antibiotics, Antineoplastic; D017239:Paclitaxel; D020123:Sirolimus