Association of adventitial vasa vasorum and inflammation with coronary hyperconstriction after drug-eluting stent implantation in pigs in vivo

Kensuke Nishimiya, Yasuharu Matsumoto, Tomohiko Shindo, Kenichiro Hanawa, Yuhi Hasebe, Ryuji Tsuburaya, Takashi Shiroto, Jun Takahashi, Kenta Ito, Hatsue Ishibashi-Ueda, Satoshi Yasuda, Hiroaki Shimokawa

Research output: Contribution to journalArticle

22 Citations (Scopus)

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. Methods and 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.

Original languageEnglish
Pages (from-to)1787-1798
Number of pages12
JournalCirculation Journal
Volume79
Issue number8
DOIs
Publication statusPublished - 2015 Jul 24

Keywords

  • Adventitia
  • Rho-kinase
  • Spasm
  • Stents
  • Vasoconstriction

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine

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