title: A new rapamycin-abluminally coated chitosan/heparin stent system accelerates early re-endothelialisation and improves anti-coagulant properties in porcine coronary artery models.
abstract: OBJECTIVE
  Drug-eluting stents (DES) in percutaneous coronary intervention are more effective in preventing in-stent restenosis compared with bare metal stents (BMS); however, DES may cause late stent thrombosis, which has limited its use. In this study, the functional properties of a newly developed DES (RAP/CS/HEP), in which rapamycin was abluminally-loaded onto a chitosan/heparin coating stent (CS/HEP), were investigated in large animal artery injury models.
  
  
  METHODS
  The effectiveness of BMS, RAP (the traditional version of rapamycin DES), CS/HEP and RAP/CS/HEP stents in preventing coagulation and promoting re-endothelialisation was examined and compared in the porcine coronary artery models with arteriovenous shunt, high load thrombus and coronary balloon injury at day 7 and 28, respectively, after stent implantation. The re-endothelialisation on these stents was further evaluated in terms of endothelial gene expression using quantitative RT-PCR.
  
  
  RESULTS
  In the porcine coronary artery injury models, both RAP and RAP/CS/HEP stents were potent in reducing neointimal thickness, thus enlarging lumen area efficiently in the stented artery region compared with BMS and CS/HEP. RAP/CS/HEP stents facilitated re-endothelialisation and inhibited thrombosis more efficiently than BMS and RAP. Consistent with this, the expression of endothelial genes, such as CD31, CD34, eNOS and VEGF, was significantly elevated with RAP/CS/HEP stents compared with RAP and BMS stents.
  
  
  CONCLUSIONS
  Abluminal coating of rapamycin onto the endothelialisation-accelerated CS/HEP stent and may prove to be an efficient treatment for tackling the late stent thrombosis associated with the traditionally circumferential RAP stent. This new RAP/CS/HEP stent system exhibits considerably improved therapeutic activity.
authors.affiliation: . email@email.com.
authors.forename: Junqing Q
authors.initials: JQ
authors.lastname: Gao
authors.forename: Jianpu P
authors.initials: JP
authors.lastname: Zheng
authors.forename: Huigen G
authors.initials: HG
authors.lastname: Jin
authors.forename: Wenquan Q
authors.initials: WQ
authors.lastname: Zhang
authors.forename: Pengyong Y
authors.initials: PY
authors.lastname: Yan
authors.forename: Tao
authors.initials: T
authors.lastname: Chen
authors.forename: Zongjun J
authors.initials: ZJ
authors.lastname: Liu
mesh_terms: D000818:Animals; D000925:Anticoagulants / Q000494:pharmacology*; D001672:Biocompatible Materials / Q000494:pharmacology*; D048271:Chitosan / Q000494:pharmacology*; D003324:Coronary Artery Disease / Q000628:therapy*; D003331:Coronary Vessels / Q000293:injuries*; D004195:Disease Models, Animal; D054855:Drug-Eluting Stents; D006493:Heparin / Q000494:pharmacology*; D007166:Immunosuppressive Agents / Q000494:pharmacology*; D020123:Sirolimus / Q000494:pharmacology*; D013552:Swine
chemical_list: D000925:Anticoagulants; D001672:Biocompatible Materials; D007166:Immunosuppressive Agents; D006493:Heparin; D048271:Chitosan; D020123:Sirolimus