title: Association of Adventitial Vasa Vasorum and Inflammation With Coronary Hyperconstriction After Drug-Eluting Stent Implantation in Pigs In Vivo.
abstract: BACKGROUND
  The importance of adventitial inflammation has been implicated for the pathogenesis of coronary artery disease. However, the roles of adventitial changes in drug-eluting stent (DES)-induced coronary hyperconstriction remain largely unknown. In the present study, this issue in pigs in vivo with a special reference to adventitial vasa vasorum (VV) formation and Rho-kinase activation, a central mechanism of coronary vasospasm, was examined.
  
  
  RESULTS
  Each animal received a sirolimus-eluting stent (SES) and a biolimus A9-eluting stent (BES), one in the left anterior descending and another in the left circumflex coronary arteries in a randomized manner (n=18). After 1, 3 and 6 months, coronary vasomotion was examined. At 1 month, coronary vasoconstriction to serotonin was significantly enhanced at the SES edges as compared with the BES edges (SES, 52±7% vs. BES, 22±3%, P<0.01), which was equally prevented by a selective Rho-kinase inhibitor, hydroxyfasudil. A significant difference in vasoconstriction between SES and BES was sustained for 6 months. A micro-CT showed VV augmentation at the SES site, extending to the proximal and distal edges. Immunostainings demonstrated that VV formation, macrophage infiltration in the adventitia and Rho-kinase expressions/activation were significantly enhanced at the SES edges as compared with the BES edges.
  
  
  CONCLUSIONS
  The DES with durable polymers enhances VV formation and inflammation in the adventitia, associating with the pathogenesis of DES-induced coronary hyperconstriction through Rho-kinase activation in pigs in vivo.
authors.affiliation: Department of Cardiovascular Medicine, Tohoku University Graduate School of Medicine.
authors.forename: Kensuke
authors.initials: K
authors.lastname: Nishimiya
authors.forename: Yasuharu
authors.initials: Y
authors.lastname: Matsumoto
authors.forename: Tomohiko
authors.initials: T
authors.lastname: Shindo
authors.forename: Kenichiro
authors.initials: K
authors.lastname: Hanawa
authors.forename: Yuhi
authors.initials: Y
authors.lastname: Hasebe
authors.forename: Ryuji
authors.initials: R
authors.lastname: Tsuburaya
authors.forename: Takashi
authors.initials: T
authors.lastname: Shiroto
authors.forename: Jun
authors.initials: J
authors.lastname: Takahashi
authors.forename: Kenta
authors.initials: K
authors.lastname: Ito
authors.forename: Hatsue
authors.initials: H
authors.lastname: Ishibashi-Ueda
authors.forename: Satoshi
authors.initials: S
authors.lastname: Yasuda
authors.forename: Hiroaki
authors.initials: H
authors.lastname: Shimokawa
mesh_terms: D000818:Animals; D003329:Coronary Vasospasm / Q000201:enzymology* / Q000209:etiology / Q000473:pathology / Q000503:physiopathology; D054855:Drug-Eluting Stents / Q000009:adverse effects*; D004789:Enzyme Activation / Q000187:drug effects; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects*; D020123:Sirolimus / Q000009:adverse effects* / Q000494:pharmacology; D013552:Swine; D014651:Vasa Vasorum / Q000201:enzymology* / Q000473:pathology / Q000503:physiopathology; D054460:rho-Associated Kinases / Q000096:biosynthesis*
chemical_list: D054460:rho-Associated Kinases; D020123:Sirolimus