Circulation Journal Official Journal of the Japanese Circulation Society http://www. j-circ.or.jpIn order to reduce the adverse effects of the first-generation DES, many efforts have been made, including the development of a newer biocompatible DES. 9 Biolimus-A9 eluting stent (BES) is one of the new-generation DES with unique characteristics, such as biodegradable polymers that are absorbed into the arterial wall approximately 6 months after stent implantation. 9-11 Although BES has recently been shown to preserve ex-vivo coronary vasomotion as compared with SES in the short-term observations in pigs 12 and humans, 7 its mechanism remains largely unknown.We have previously demonstrated that Rho-kinase activation is a central molecular mechanism of coronary spasm in he widespread utilization of drug-eluting stents (DES) has remarkably reduced the risk of re-stenosis and of repeated revascularization. 1 However, the first-generation DES with durable polymers, such as sirolimus-eluting stents (SES), have no beneficial prognostic effects as compared with bare metal stents 2 or even cause unfavorable effects, such as stent thrombosis 3,4 and coronary hyperconstricting responses, 5-8 not only to acetylcholine, 5 but also to exercise 6 and atrial pacing. 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.