Involvement of rho-kinase activation in the pathogenesis of coronary hyperconstricting responses induced by drug-eluting stents in patients with coronary artery disease.

Abstract

BACKGROUND:

Activation of Rho-kinase plays a central role in the pathogenesis of drug-eluting stents (DES)-induced coronary hyperconstricting responses in pigs in vivo has been previously demonstrated. In the present study, Rho-kinase activation involved in those responses in patients with coronary artery disease (CAD) is examined.

METHODS AND RESULTS:

In 24 patients with CAD who underwent coronary intervention with either DES or bare-metal stents (BMS), coronary vasomotor responses to intracoronary acetylcholine (ACh) before and after intracoronary pre-treatment with a Rho-kinase inhibitor, fasudil was examined. Coronary vasomotor responses by quantitative coronary angiography (QCA) and coronary vascular structure by optical coherence tomography (OCT) was evaluated. QCA showed that the coronary vasoconstricting responses to ACh were significantly enhanced in the DES group compared with the BMS group both at the proximal and the distal segments adjacent to the stents (proximal: BMS -13.0±10.7% vs. DES -25.4±14.3%, P=0.036; distal: BMS -24.4±12.2% vs. DES -43.8±14.7%, P=0.003). Importantly, fasudil markedly attenuated the enhanced vasoconstricting responses to ACh in the DES group (proximal 10.2±11.7%, distal 14.4±10.5% vs. before fasudil, both P<0.01). In the OCT imaging analysis, there was no significant correlation between intimal thickness and coronary vasoconstriction to ACh.

CONCLUSIONS:

These results indicate that Rho-kinase activation is substantially involved in the pathogenesis of the DES-induced coronary hyperconstricting responses in patients with CAD, suggesting the therapeutic importance of Rho-kinase pathway.

• Authors: Kentaro Aizawa, Satoshi Yasuda, Jun Takahashi, Toru Takii, Yoku Kikuchi, Ryuji Tsuburaya, Yoshitaka Ito, Kenta Ito, Masaharu Nakayama, Morihiko Takeda, Hiroaki Shimokawa
• Journal: Circulation journal : official journal of the Japanese Circulation Society (Circ J) Vol. 76 Issue 11 Pg. 2552-60 ( 2012) ISSN: 1347-4820 [Electronic] Japan
• PMID: 22813839 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• rho-Associated Kinases

Topics

• Aged
• Aged, 80 and over
• Coronary Angiography
• Coronary Artery Disease (enzymology, pathology, physiopathology, surgery)
• Coronary Restenosis (enzymology, pathology, physiopathology)
• Drug-Eluting Stents
• Enzyme Activation
• Female
• Follow-Up Studies
• Humans
• Male
• Middle Aged
• Vasoconstriction
• rho-Associated Kinases (metabolism)