Association of Adventitial Vasa Vasorum and Inflammation With Coronary Hyperconstriction After Drug-Eluting Stent Implantation in Pigs In Vivo

作者：Nishimiya Kensuke; Matsumoto Yasuharu; Shindo Tomohiko; Hanawa Kenichiro; Hasebe Yuhi; Tsuburaya Ryuji; Shiroto Takashi; Takahashi Jun; Ito Kenta; Ishibashi Ueda Hatsue; Yasuda Satoshi; Shimokawa Hiroaki^*

来源：Circulation Journal, 2015, 79(8): 1787-U401.

DOI：10.1253/circj.CJ-15-0149

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

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.

• 出版日期2015-8