A novel IKK inhibitor prevents progression of restenosis after arterial injury in mice.
Restenosis after percutaneous coronary intervention (PCI) is still a clinically serious problem. We examined the treatment efficacy of IMD-0354, a novel IKK inhibitor, on arteriopathy. Using C57BL/6J mice, a wire-injury model was prepared and the mice were intraperitoneally injected with IMD-0354 or vehicle twice a day. The vehicle-treated injured arteries showed significantly thickened intima (3.77 ± 0.59, n = 8), however, IMD-0354 suppressed its progression (1.62 ± 0.22, n = 10, P < 0.05) on day 28. While enhanced expression of PCNA and NF-κB was observed in the untreated injured arteries, IMD-0354 significantly suppressed their expressions. Quantitative RT-PCR revealed that the expression of several inflammatory factors was reduced in the arteries from mice which received IMD-0354 treatment compared with the control animals. Thus, this drug may effectively prevent restenosis after coronary intervention and other cardiovascular diseases.
Department of Cardiovascular Medicine, Tokyo Medical and Dental University, Japan.
Rikuta
R
Hamaya
Masahito
M
Ogawa
Naho
N
Kobayashi
Jun-Ichi
J
Suzuki
Akiko
A
Itai
Yasunobu
Y
Hirata
Ryozo
R
Nagai
Mitsuaki
M
Isobe
D015906:Angioplasty, Balloon, Coronary; D000818:Animals; D001549:Benzamides / Q000008:administration & dosage*; D015153:Blotting, Western; D049109:Cell Proliferation / Q000187:drug effects; D016207:Cytokines / Q000187:drug effects / Q000378:metabolism; D004195:Disease Models, Animal; D018450:Disease Progression; D005263:Femoral Artery / Q000293:injuries*; D005455:Fluorescent Antibody Technique; D006083:Graft Occlusion, Vascular / Q000517:prevention & control*; D051550:I-kappa B Kinase / Q000037:antagonists & inhibitors*; D007150:Immunohistochemistry; D007274:Injections, Intraperitoneal; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D011183:Postoperative Complications; D018809:Proliferating Cell Nuclear Antigen / Q000187:drug effects / Q000378:metabolism; D060888:Real-Time Polymerase Chain Reaction; D016896:Treatment Outcome; D017539:Tunica Intima / Q000187:drug effects / Q000473:pathology; D057772:Vascular System Injuries / Q000628:therapy*
D001549:Benzamides; D016207:Cytokines; D018809:Proliferating Cell Nuclear Antigen; C492919:N-(3,5-bis(trifluoromethyl)phenyl)-5-chloro-2-hydroxybenzamide; D051550:I-kappa B Kinase