Involvement of Rho-Kinase Activation in the Pathogenesis of Coronary Hyperconstricting Responses Induced by Drug-Eluting Stents in Patients With Coronary Artery Disease

Abstract

Circulation Journal Official Journal of the Japanese Circulation Society http://www. j-circ.or.jp are-metal stents (BMS) and, more recently, drug-eluting stents (DES), such as sirolimus-eluting (Cypher TM ) and paclitaxel-eluting stents (Taxus TM ), have further improved early results and reduced the risk of restenosis. 1,2 However, DES have also not been shown to improve longterm survival of patients with coronary artery disease (CAD) compared with BMS. 3 Moreover, there is a concern on the safety issues of DES, given the potential for late stent thrombosis, especially after discontinuation of dual antiplatelet therapy. 4 Another concern is the DES-induced impairment of coronary vasomotion. 5-10 Indeed, enhanced coronary vasoconstriction in response to acetylcholine (ACh) 5-8 or exercise 9 was demonstrated in the coronary segments adjacent to DES, but not in those adjacent to BMS, and sudden cardiac arrest was reported among patients with severe coronary vasospasm following DES implantation. 10 Patients implanted with DES have a higher rate of positive exercise stress test than patients implanted with BMS 1 month after percutaneous coronary intervention (PCI), 11 which might also indicate DES-induced vasomotor dysfunction. Editorial p 2536Rho-kinase is one of the downstream effectors of the small

Guidelines for Diagnosis and Treatment of Patients With Vasospastic Angina (Coronary Spastic Angina) (JCS 2013)

“…288,289 Recent studies in a porcine model and in patients with coronary artery disease have suggested that Rho-kinase, a molecular switch that regulates vascular smooth muscle contraction, plays an important role in the pathogenesis of coronary dysfunction after DES implantation, and that DES induces smooth muscle dysfunction as well as endothelial dysfunction. 290, 291 These findings suggest that vascular dysfunction following DES implantation is an important target for clinical intervention.…”

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

“…15, 16 Quantitative coronary angiography (QCA) (INFX-8000V; Toshiba Medical Co, Tokyo, Japan) was performed in a blind manner at the proximal and distal stent edge segments adjacent to the stent (5 mm apart from the proximal and distal stent end portions), as previously described. 5 animals and humans, 8,13, 14 and that it also plays a key role in the pathogenesis of coronary hyperconstricting responses after the first-generation DES implantation in animals 15, 16 and humans 5 as compared with the bare-metal stents. Nevertheless, it remains to be elucidated why DES-induced coronary hyperconstriction spontaneously develops at the proximal and distal stent edges.…”

Rho-Kinase Pathway

“…However, the authors performed OCT imaging analysis to provide detailed information on the intimal area of the coronary artery. 7 The results demonstrated a lack of correlation between intimal hyperplasia and DES-induced coronary hyperconstrictive response. This result is consistent with the previous finding that coronary vasospasm is associated with a variable degree of intimal hyperplasia in a swine model of coronary vasospasm.…”