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.

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.

• Authors: 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
• Journal: Circulation journal : official journal of the Japanese Circulation Society (Circ J) Vol. 79 Issue 8 Pg. 1787-98 ( 2015) ISSN: 1347-4820 [Electronic] Japan
• PMID: 26027445 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• rho-Associated Kinases
• Sirolimus

Topics

• Animals
• Coronary Vasospasm (enzymology, etiology, pathology, physiopathology)
• Drug-Eluting Stents (adverse effects)
• Enzyme Activation (drug effects)
• Gene Expression Regulation, Enzymologic (drug effects)
• Sirolimus (adverse effects, pharmacology)
• Swine
• Vasa Vasorum (enzymology, pathology, physiopathology)
• rho-Associated Kinases (biosynthesis)