Rapamycin inhibits re-endothelialization after percutaneous coronary intervention by impeding the proliferation and migration of endothelial cells and inducing apoptosis of endothelial progenitor cells.
Endothelial-cell function is important in the healing of damaged endothelium after percutaneous coronary artery damage. In 3 different animal models, we sought to determine whether rapamycin (sirolimus) affects the proliferation and migration of endothelial cells and endothelial progenitor cells. First, after we implanted stents in dogs, we found that re-endothelialization was impeded more by drug-eluting stents than by bare-metal stents, 30 days after percutaneous coronary intervention. Second, in vitro in rats, we found that 1-100 ng/mL of rapamycin time- and dose-dependently inhibited proliferation over 72 hr (with effects evident as early as 24 hr) and also dose-dependently induced endothelial progenitor-cell apoptosis. Finally, in vivo in rats, we observed that vascular endothelial growth factor expression was decreased after 5 days of rapamycin treatment. We conclude that rapamycin impedes re-endothelialization after drug-eluting stent implantation by inhibiting the proliferation and migration of coronary endothelial cells, inducing endothelial progenitor-cell apoptosis, and decreasing vascular endothelial growth factor expression in the circulation.
Liu
Hai-Tao
HT
Department of Cardiology, Xijing Hospital, Fourth Military Medical University, Xi'an, Shaanxi 710032, People's Republic of China.
Li
Fei
F
Wang
Wen-Yong
WY
Li
Xiao-Jing
XJ
Liu
Yi-Meng
YM
Wang
Rui-An
RA
Guo
Wen-Yi
WY
Wang
Hai-Chang
HC
D015906:Angioplasty, Balloon, Coronary / Q000295:instrumentation*; D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D002317:Cardiovascular Agents / Q000008:administration & dosage*; D002465:Cell Movement / Q000187:drug effects*; D049109:Cell Proliferation / Q000187:drug effects*; D002478:Cells, Cultured; D004285:Dogs; D004305:Dose-Response Relationship, Drug; D054855:Drug-Eluting Stents; D042783:Endothelial Cells / Q000187:drug effects* / Q000473:pathology; D008297:Male; D008670:Metals; D023421:Models, Animal; D011474:Prosthesis Design; D051381:Rats; D017207:Rats, Sprague-Dawley; D020123:Sirolimus / Q000008:administration & dosage*; D013234:Stem Cells / Q000187:drug effects* / Q000473:pathology; D015607:Stents; D013997:Time Factors; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism
D002317:Cardiovascular Agents; D008670:Metals; D042461:Vascular Endothelial Growth Factor A; C467498:vascular endothelial growth factor A, rat; D020123:Sirolimus
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