title: Vascular healing in drug-eluting stents: differential drug-associated response of limus-eluting stents in a preclinical model of stent implantation.
abstract: OBJECTIVE
  We aimed to assess the influence of different sirolimus analogues released from a uniform stent platform on re-endothelialisation and vascular healing responses.
  
  
  RESULTS
  Bare metal stents (BMS) were coated with a fluoropolymer containing everolimus (EES), sirolimus (SES) or zotarolimus (ZES) to generate drug-eluting stents (DES) with identical stent backbones, drug loads and release kinetics. DES constructs and control BMS were implanted into the iliac arteries of rabbits and were analysed at 14 days by scanning electron microscopy (SEM) and confocal microscopy for en face evaluation of endothelialisation (n=6 for each stent), or at 28 days to determine histomorphometric characteristics (n=11 for each stent). SEM analysis revealed low degrees of strut re-endothelialisation within the DES without differences among groups, while the BMS control showed almost complete endothelialisation. Percent stenosis was significantly reduced in all DES compared to BMS. Strut-based fibrin analysis revealed significantly greater deposition in the DES compared to BMS, with EES showing maximum fibrin deposition among the DES groups.
  
  
  CONCLUSIONS
  Sirolimus and its derivatives have similar effects on endothelial regrowth and neointimal thickening. The observation of greatest fibrin deposition in the experimental EES group indicates that everolimus may affect vascular healing differently.
authors.affiliation: Deutsches Herzzentrum München and Medizinische Klinik, Klinikum rechts der Isar, Technische Universität München, München, Germany.
authors.forename: Kristin
authors.initials: K
authors.lastname: Steigerwald
authors.forename: Simone
authors.initials: S
authors.lastname: Ballke
authors.forename: Shawn Chin
authors.initials: SC
authors.lastname: Quee
authors.forename: Robert A
authors.initials: RA
authors.lastname: Byrne
authors.forename: Marc
authors.initials: M
authors.lastname: Vorpahl
authors.forename: Michael
authors.initials: M
authors.lastname: Vogeser
authors.forename: Frank
authors.initials: F
authors.lastname: Kolodgie
authors.forename: Renu
authors.initials: R
authors.lastname: Virmani
authors.forename: Michael
authors.initials: M
authors.lastname: Joner
mesh_terms: D000800:Angioplasty, Balloon / Q000009:adverse effects / Q000295:instrumentation*; D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D002317:Cardiovascular Agents / Q000008:administration & dosage*; D054855:Drug-Eluting Stents; D042783:Endothelial Cells / Q000473:pathology; D000068338:Everolimus; D005337:Fibrin / Q000378:metabolism; D007083:Iliac Artery / Q000378:metabolism / Q000473:pathology* / Q000648:ultrastructure; D007150:Immunohistochemistry; D008297:Male; D008670:Metals; D018613:Microscopy, Confocal; D008855:Microscopy, Electron, Scanning; D023421:Models, Animal; D058426:Neointima; D019408:Platelet Endothelial Cell Adhesion Molecule-1 / Q000378:metabolism; D011474:Prosthesis Design; D011817:Rabbits; D020123:Sirolimus / Q000008:administration & dosage / Q000031:analogs & derivatives*; D013997:Time Factors; D014945:Wound Healing
chemical_list: D015415:Biomarkers; D002317:Cardiovascular Agents; D008670:Metals; D019408:Platelet Endothelial Cell Adhesion Molecule-1; D005337:Fibrin; D000068338:Everolimus; C489443:zotarolimus; D020123:Sirolimus