title: Biodegradable Polymers Influence the Effect of Atorvastatin on Human Coronary Artery Cells.
abstract: Drug-eluting stents (DES) have reduced in-stent-restenosis drastically. Yet, the stent surface material directly interacts with cascades of biological processes leading to an activation of cellular defense mechanisms. To prevent adverse clinical implications, to date almost every patient with a coronary artery disease is treated with statins. Besides their clinical benefit, statins exert a number of pleiotropic effects on endothelial cells (ECs). Since maintenance of EC function and reduction of uncontrolled smooth muscle cell (SMC) proliferation represents a challenge for new generation DES, we investigated the effect of atorvastatin (ATOR) on human coronary artery cells grown on biodegradable polymers. Our results show a cell type-dependent effect of ATOR on ECs and SMCs. We observed polymer-dependent changes in IC50 values and an altered ATOR-uptake leading to an attenuation of statin-mediated effects on SMC growth. We conclude that the selected biodegradable polymers negatively influence the anti-proliferative effect of ATOR on SMCs. Hence, the process of developing new polymers for DES coating should involve the characterization of material-related changes in mechanisms of drug actions.
authors.affiliation: Department of Internal Medicine B (Cardiology), University Medicine Greifswald, Ferdinand-Sauerbruch-Strasse, 17475 Greifswald, Germany. strohbac@uni-greifswald.de.|DZHK (German Centre for Cardiovascular Research), Partner Site Greifswald, University Medicine Greifswald, 17475 Greifswald, Germany. strohbac@uni-greifswald.de.
authors.forename: Anne
authors.initials: A
authors.lastname: Strohbach
authors.affiliation: Institute of Pharmacology, University Medicine Greifswald, Felix-Hausdorff-Strasse 3, 17477 Greifswald, Germany. begunk@gmx.de.
authors.forename: Robert
authors.initials: R
authors.lastname: Begunk
authors.affiliation: Faculty of Engineering and Informatics, Osnabrück University of Applied Sciences, Albrechtstrasse 30, 49076 Osnabrück, Germany. s.petersen@hs-osnabrueck.de.
authors.forename: Svea
authors.initials: S
authors.lastname: Petersen
authors.affiliation: Department of Internal Medicine B (Cardiology), University Medicine Greifswald, Ferdinand-Sauerbruch-Strasse, 17475 Greifswald, Germany. felix@uni-greifswald.de.|DZHK (German Centre for Cardiovascular Research), Partner Site Greifswald, University Medicine Greifswald, 17475 Greifswald, Germany. felix@uni-greifswald.de.
authors.forename: Stephan B
authors.initials: SB
authors.lastname: Felix
authors.affiliation: Research & Development, Aesculap AG, Am Aesculap Platz, 78532 Tuttlingen, Germany. katrin.sternberg@aesculap.de.
authors.forename: Katrin
authors.initials: K
authors.lastname: Sternberg
authors.affiliation: Department of Internal Medicine B (Cardiology), University Medicine Greifswald, Ferdinand-Sauerbruch-Strasse, 17475 Greifswald, Germany. buschr@uni-greifswald.de.|DZHK (German Centre for Cardiovascular Research), Partner Site Greifswald, University Medicine Greifswald, 17475 Greifswald, Germany. buschr@uni-greifswald.de.
authors.forename: Raila
authors.initials: R
authors.lastname: Busch
mesh_terms: D000069059:Atorvastatin / Q000494:pharmacology*; D063566:Biodegradable Plastics / Q000494:pharmacology*; D018929:Cell Culture Techniques; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D003324:Coronary Artery Disease / Q000188:drug therapy; D003331:Coronary Vessels / Q000166:cytology* / Q000187:drug effects; D054855:Drug-Eluting Stents; D042783:Endothelial Cells / Q000166:cytology / Q000187:drug effects; D006801:Humans; D032389:Myocytes, Smooth Muscle / Q000166:cytology / Q000187:drug effects*; D009928:Organ Specificity; D011108:Polymers / Q000494:pharmacology*; D013499:Surface Properties
chemical_list: D063566:Biodegradable Plastics; D011108:Polymers; D000069059:Atorvastatin
keywords: ">l-lactide); atorvastatin; biodegradable polymer; human coronary artery endothelial cells; human coronary artery smooth muscle cells; poly(