TY - JOUR
T1 - Endothelial progenitor cell response to antiproliferative drug exposure
AU - Banerjee, Subhash
AU - Xu, Hao
AU - Fuh, Eric
AU - Nguyen, Kytai T.
AU - Garcia, Joseph A
AU - Brilakis, Emmanouil S
AU - Bhatt, Deepak L.
N1 - Funding Information:
S Banerjee has received speaker honoraria from Medtronic, Covidien and research support from Medicines Company and Gilead ; DL Bhatt is on the advisory board of: Medscape Cardiology; board of directors: Boston VA Research Institute, Society of Chest Pain Centers; chair: American Heart Association Get With The Guidelines Science Subcommittee; honoraria: American College of Cardiology (Editor, Clinical Trials, Cardiosource), Duke Clinical Research Institute (clinical trial steering committees), Slack Publications (Chief Medical Editor, Cardiology Today Intervention), WebMD (CME steering committees); research grants: Amarin, AstraZeneca, Bristol-Myers Squibb, Eisai, Ethicon, Medtronic, Sanofi Aventis, The Medicines Company; unfunded research: PLx Pharma, Takeda. H Xu, E Fuh, KT Nguyen, JA Garcia have no disclosures.
PY - 2012/11
Y1 - 2012/11
N2 - Background: Vascular stent coverage by endothelial cells, derived from endothelial progenitor cells (EPC) is considered a surrogate for healing. However, the effects of antiproliferative drugs used in current drug-eluting stents (DES) on EPC proliferative and antithrombotic function remains poorly defined. Method and results: Herein, we studied and compared the in vitro and in vivo effects of four antiproliferative drugs - paclitaxel, sirolimus, everolimus, and zotarolimus on several EPC properties including colony forming units (CFU), cell proliferation, apoptosis, antithrombotic and prothrombotic gene expression and nitric oxide (NO) as well as prostacyclin (PGI2) release. We also examined EPC migration and adhesion under flow conditions. We find that whereas all antiproliferative agents inhibited EPC proliferation and caused cell apoptosis, only paclitaxel and sirolimus reduced CFU formation. Paclitaxel treatment also resulted in the greatest down-regulation of antithrombotic gene expression and up-regulation of prothrombotic gene expression. NO release, migration, and adhesion of EPC under shear stress were inhibited by all antiproliferative drugs, most notably by paclitaxel and sirolimus. Conclusions: These results indicate that antiproliferative drugs on DES, particularly paclitaxel, impair the proliferative and antithrombotic functions of EPC, and thereby could contribute to incomplete vascular healing and increase the risk of stent thrombosis.
AB - Background: Vascular stent coverage by endothelial cells, derived from endothelial progenitor cells (EPC) is considered a surrogate for healing. However, the effects of antiproliferative drugs used in current drug-eluting stents (DES) on EPC proliferative and antithrombotic function remains poorly defined. Method and results: Herein, we studied and compared the in vitro and in vivo effects of four antiproliferative drugs - paclitaxel, sirolimus, everolimus, and zotarolimus on several EPC properties including colony forming units (CFU), cell proliferation, apoptosis, antithrombotic and prothrombotic gene expression and nitric oxide (NO) as well as prostacyclin (PGI2) release. We also examined EPC migration and adhesion under flow conditions. We find that whereas all antiproliferative agents inhibited EPC proliferation and caused cell apoptosis, only paclitaxel and sirolimus reduced CFU formation. Paclitaxel treatment also resulted in the greatest down-regulation of antithrombotic gene expression and up-regulation of prothrombotic gene expression. NO release, migration, and adhesion of EPC under shear stress were inhibited by all antiproliferative drugs, most notably by paclitaxel and sirolimus. Conclusions: These results indicate that antiproliferative drugs on DES, particularly paclitaxel, impair the proliferative and antithrombotic functions of EPC, and thereby could contribute to incomplete vascular healing and increase the risk of stent thrombosis.
KW - Antiproliferative drugs
KW - Drug-eluting stent
KW - Endothelial progenitor cell
UR - http://www.scopus.com/inward/record.url?scp=84867874811&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84867874811&partnerID=8YFLogxK
U2 - 10.1016/j.atherosclerosis.2012.08.025
DO - 10.1016/j.atherosclerosis.2012.08.025
M3 - Article
C2 - 22959701
AN - SCOPUS:84867874811
SN - 0021-9150
VL - 225
SP - 91
EP - 98
JO - Atherosclerosis
JF - Atherosclerosis
IS - 1
ER -