title: Targeting In-Stent-Stenosis with RGD- and CXCL1-Coated Mini-Stents in Mice.
abstract: Atherosclerotic lesions that critically narrow the artery can necessitate an angioplasty and stent implantation. Long-term therapeutic effects, however, are limited by excessive arterial remodeling. We here employed a miniaturized nitinol-stent coated with star-shaped polyethylenglycole (star-PEG), and evaluated its bio-functionalization with RGD and CXCL1 for improving in-stent stenosis after implantation into carotid arteries of mice. Nitinol foils or stents (bare metal) were coated with star-PEG, and bio-functionalized with RGD, or RGD/CXCL1. Cell adhesion to star-PEG-coated nitinol foils was unaltered or reduced, whereas bio-functionalization with RGD but foremost RGD/CXCL1 increased adhesion of early angiogenic outgrowth cells (EOCs) and endothelial cells but not smooth muscle cells when compared with bare metal foils. Stimulation of cells with RGD/CXCL1 furthermore increased the proliferation of EOCs. In vivo, bio-functionalization with RGD/CXCL1 significantly reduced neointima formation and thrombus formation, and increased re-endothelialization in apoE-/- carotid arteries compared with bare-metal nitinol stents, star-PEG-coated stents, and stents bio-functionalized with RGD only. Bio-functionalization of star-PEG-coated nitinol-stents with RGD/CXCL1 reduced in-stent neointima formation. By supporting the adhesion and proliferation of endothelial progenitor cells, RGD/CXCL1 coating of stents may help to accelerate endothelial repair after stent implantation, and thus may harbor the potential to limit the complication of in-stent restenosis in clinical approaches.
authors.affiliation: Institute for Molecular Cardiovascular Research, University Hospital Aachen, RWTH Aachen University, Aachen, Germany.|Institute of Technical and Macromolecular Chemistry, RWTH Aachen University, Aachen, Germany.|Biochemistry Institute, Justus-Liebig-University, Giessen, Germany.
authors.forename: Sakine
authors.initials: S
authors.lastname: Simsekyilmaz
authors.affiliation: Institute for Molecular Cardiovascular Research, University Hospital Aachen, RWTH Aachen University, Aachen, Germany.|Human Genetic Laboratory, University of Medicine and Pharmacy, Craiova, Romania.|IZKF Aachen, University Hospital Aachen, RWTH Aachen University, Aachen, Germany.
authors.forename: Elisa A
authors.initials: EA
authors.lastname: Liehn
authors.affiliation: Institute of Technical and Macromolecular Chemistry, RWTH Aachen University, Aachen, Germany.|Department of Applied Medical Engineering, Helmholtz Institute for Biomedical Engineering, RWTH Aachen University, Aachen, Germany.
authors.forename: Stefan
authors.initials: S
authors.lastname: Weinandy
authors.affiliation: Institute for Textile Technology, RWTH Aachen University, Aachen, Germany.
authors.forename: Fabian
authors.initials: F
authors.lastname: Schreiber
authors.affiliation: Institute for Cardiovascular Prevention, Ludwig-Maximilians University Munich, Munich, Germany.
authors.forename: Remco T A
authors.initials: RT
authors.lastname: Megens
authors.affiliation: Institute for Molecular Cardiovascular Research, University Hospital Aachen, RWTH Aachen University, Aachen, Germany.
authors.forename: Wendy
authors.initials: W
authors.lastname: Theelen
authors.affiliation: Department of Oral and Maxillofacial Surgery, Center of Clinical Neurosciences, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
authors.forename: Ralf
authors.initials: R
authors.lastname: Smeets
authors.affiliation: Department of Applied Medical Engineering, Helmholtz Institute for Biomedical Engineering, RWTH Aachen University, Aachen, Germany.
authors.forename: Stefan
authors.initials: S
authors.lastname: Jockenhövel
authors.affiliation: Institute for Textile Technology, RWTH Aachen University, Aachen, Germany.
authors.forename: Thomas
authors.initials: T
authors.lastname: Gries
authors.affiliation: Institute of Technical and Macromolecular Chemistry, RWTH Aachen University, Aachen, Germany.
authors.forename: Martin
authors.initials: M
authors.lastname: Möller
authors.affiliation: Institute of Technical and Macromolecular Chemistry, RWTH Aachen University, Aachen, Germany.
authors.forename: Doris
authors.initials: D
authors.lastname: Klee
authors.affiliation: Institute for Cardiovascular Prevention, Ludwig-Maximilians University Munich, Munich, Germany.
authors.forename: Christian
authors.initials: C
authors.lastname: Weber
authors.affiliation: Institute for Experimental Biomedicine, University Hospital Würzburg, Würzburg, Germany.
authors.forename: Alma
authors.initials: A
authors.lastname: Zernecke
mesh_terms: D000497:Alloys / Q000737:chemistry; D000818:Animals; D016893:Carotid Stenosis / Q000209:etiology / Q000517:prevention & control*; D002448:Cell Adhesion / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D054360:Chemokine CXCL1 / Q000737:chemistry / Q000494:pharmacology*; D004730:Endothelium, Vascular / Q000187:drug effects* / Q000502:physiology; D051379:Mice; D009842:Oligopeptides / Q000737:chemistry / Q000494:pharmacology*; D015607:Stents / Q000009:adverse effects*
chemical_list: D000497:Alloys; D054360:Chemokine CXCL1; D009842:Oligopeptides; C013616:nitinol; C047981:arginyl-glycyl-aspartic acid