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The integrin ligand c(RGDf(NMe)Nal) reduces neointimal hyperplasia in a polymer-free drug-eluting stent system
dc.contributor.author | Rechenmacher, Florian |
dc.contributor.author | Steigerwald, Kristin |
dc.contributor.author | Laufer, Burkhardt |
dc.contributor.author | Neubauer, Stefanie |
dc.contributor.author | Kapp, Tobias G. |
dc.contributor.author | Li, Liang |
dc.contributor.author | Mas Moruno, Carlos |
dc.contributor.author | Joner, Michael |
dc.contributor.author | Kessler, Horst |
dc.contributor.other | Universitat Politècnica de Catalunya. Departament de Ciència dels Materials i Enginyeria Metal·lúrgica |
dc.date.accessioned | 2014-09-22T09:41:31Z |
dc.date.created | 2014-07-01 |
dc.date.issued | 2014-07-01 |
dc.identifier.citation | Rechenmacher, F. [et al.]. The integrin ligand c(RGDf(NMe)Nal) reduces neointimal hyperplasia in a polymer-free drug-eluting stent system. "Chemmedchem", 01 Juliol 2014, vol. 9, núm. 7, p. 1413-1418. |
dc.identifier.issn | 1860-7179 |
dc.identifier.uri | http://hdl.handle.net/2117/24126 |
dc.description.abstract | The use of highly active and selective integrin ligands in combination with stent implantation is emerging as a promising alternative to the release of classical immunosuppressive drugs by current drug-eluting stents (DES), which has been associated with delayed vascular healing and late stent thrombosis. Herein we present the development and biological evaluation of the integrin ligand c(RGDf(NMe)Nal) as a potent anti-proliferative molecule that targets coronary artery smooth muscle cells (CASMCs). This peptide showed an antagonistic activity for alpha v beta 3 and alpha v beta 5 in the low-nanomolar range, and selectivity against the platelet receptor alpha IIb beta 3. In vitro, it efficiently inhibited the proliferation of CASMCs, displaying higher potency than the anti-tumor drug candidate cilengitide. This peptide was then loaded into a polymer-free bare metal stent (BMS), and its release studied at different time points. Up to seven days of elution, the peptide-coated stents retained high antiproliferative activity toward CASMCs. Finally, the peptide was examined in vivo in a polymer-free DES system in a rabbit iliac artery model. After 28 days of implantation, histopathological analysis revealed that the peptide clearly decreased neointimal growth and improved vessel healing and re-endothelialization compared with the FDA-approved Cypher DES. Our study shows that this type of lipophilic integrin ligand, when eluted from a polymer-free stent system, has the potential to successfully decrease in-stent restenosis in the absence of delayed vascular healing. |
dc.format.extent | 6 p. |
dc.language.iso | eng |
dc.rights | Attribution-NonCommercial-NoDerivs 3.0 Spain |
dc.rights.uri | http://creativecommons.org/licenses/by-nc-nd/3.0/es/ |
dc.subject | Àrees temàtiques de la UPC::Enginyeria dels materials |
dc.subject.lcsh | Tissue engineering |
dc.subject.other | drug-eluting stents |
dc.subject.other | integrin ligands |
dc.subject.other | myocardial infarction |
dc.subject.other | peptides |
dc.subject.other | RGD |
dc.subject.other | smooth muscle cells |
dc.subject.other | CYCLIC-RGD PEPTIDE |
dc.subject.other | ALPHA(V)BETA(3) INTEGRIN |
dc.subject.other | BIOLOGICAL EVALUATION |
dc.subject.other | VASOMOTOR FUNCTION |
dc.subject.other | PERMANENT POLYMER |
dc.subject.other | PORCINE MODEL |
dc.subject.other | ANTAGONISTS |
dc.subject.other | ALPHA-V-BETA-3 |
dc.subject.other | SIROLIMUS |
dc.subject.other | SELECTIVITY |
dc.title | The integrin ligand c(RGDf(NMe)Nal) reduces neointimal hyperplasia in a polymer-free drug-eluting stent system |
dc.type | Article |
dc.subject.lemac | Enginyeria de teixits |
dc.contributor.group | Universitat Politècnica de Catalunya. BBT - Biomaterials, Biomecànica i Enginyeria de Teixits |
dc.identifier.doi | 10.1002/cmdc.201400078 |
dc.description.peerreviewed | Peer Reviewed |
dc.rights.access | Restricted access - publisher's policy |
local.identifier.drac | 15115093 |
dc.description.version | Postprint (published version) |
dc.date.lift | 10000-01-01 |
dc.contributor.covenantee | Technische Universität München |
dc.contributor.covenantee | Deutsches Herzzentrum München |
dc.contributor.covenantee | CVPath Institute |
local.citation.author | Rechenmacher, F.; Steigerwald, K.; Laufer, B.; Neubauer, S.; Kapp, T.; Li, L.; Mas-Moruno, C.; Joner, M.; Kessler, H. |
local.citation.publicationName | Chemmedchem |
local.citation.volume | 9 |
local.citation.number | 7 |
local.citation.startingPage | 1413 |
local.citation.endingPage | 1418 |
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