title: Atorvastatin accelerates both neointimal coverage and re-endothelialization after sirolimus-eluting stent implantation in a porcine model: new findings from optical coherence tomography and pathology.
abstract: BACKGROUND
  Delayed vessel healing after drug-eluting stent implantation is thought to be the underlying mechanisms of late stent thrombosis (LST).
  
  
  RESULTS
  In the animal model of stenting, 45 minipigs were divided into 3 groups (n=15 each): bare metal stent (BMS), sirolimus-eluting stent (SES), and SES plus atorvastatin treatment (SES+ator). Neointimal coverage and endothelium coverage were evaluated separately by optical coherence tomography (OCT), pathology, and scanning electron microscopy (SEM) at days 7, 14 and 28. OCT showed that SES significantly delayed neointimal coverage compared with BMS and the percentage of uncovered struts in the SES+ator group was significantly decreased on days 7 (42.7±1.3% vs. 56.8±5.7%, P<0.01) and 14 (24.8±4.3% vs. 45.3±2.8%, P<0.01) compared with the SES group. However, re-endothelialization was even more seriously delayed than neointima formation after SES deployment (P<0.05). Pathology and SEM revealed improved re-endothelialization of the neointima with atorvastatin therapy in terms of more struts covered by endothelium, less platelet adhesion, and higher endothelial nitric oxide synthase expression of the endothelial cells in the SES+ator group. Flow cytometry illustrated that the SES+ator group had more mobilized endothelial progenitor cells (EPCs) compared with the SES group at day 7 (0.21±0.02% vs. 0.11±0.03%, P=0.022).
  
  
  CONCLUSIONS
  Atorvastatin pretreatment can accelerate both neointimal coverage and re-endothelialization after SES implantation, which may be mediated by the mobilization of EPC and enhancement of the endothelial function of the neointima.
authors.affiliation: Department of Cardiology, State Key Laboratory of Cardiovascular Disease, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, People's Republic of China.
authors.forename: Tian-Jie
authors.initials: TJ
authors.lastname: Wang
authors.forename: Yue-Jin
authors.initials: YJ
authors.lastname: Yang
authors.forename: Bo
authors.initials: B
authors.lastname: Xu
authors.forename: Qian
authors.initials: Q
authors.lastname: Zhang
authors.forename: Chen
authors.initials: C
authors.lastname: Jin
authors.forename: Yue
authors.initials: Y
authors.lastname: Tang
authors.forename: Yi
authors.initials: Y
authors.lastname: Tian
authors.forename: Gary S
authors.initials: GS
authors.lastname: Mintz
mesh_terms: D000818:Animals; D000924:Anticholesteremic Agents / Q000494:pharmacology*; D000069059:Atorvastatin; D054855:Drug-Eluting Stents; D004730:Endothelium, Vascular / Q000378:metabolism* / Q000648:ultrastructure; D006538:Heptanoic Acids / Q000494:pharmacology*; D008855:Microscopy, Electron, Scanning; D058426:Neointima / Q000378:metabolism* / Q000473:pathology; D010973:Platelet Adhesiveness; D011758:Pyrroles / Q000494:pharmacology*; D013234:Stem Cells / Q000378:metabolism* / Q000648:ultrastructure; D013552:Swine; D041623:Tomography, Optical Coherence
chemical_list: D000924:Anticholesteremic Agents; D006538:Heptanoic Acids; D011758:Pyrroles; D000069059:Atorvastatin