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ȣ - 480108 50 |
| Potential Therapeutic Target of IKK-β in In-stent Restenosis |
| ¹Department of Internal Medicine, Chonnam National University Hospital, ²Research Institute of Medical Sciences, Chonnam National University Medical School, Gwangju, South Korea, |
| Yong-Sook Kim¹, Youngkeun Ahn¹, Hyun Kook², Sang Yup Lim¹, Kyung Ho Yun¹, Dong Goo Kang¹, Sang Hyun Lee¹, Yeon Sang Lee¹, Kye Hun Kim¹, Young Joon Hong¹, Hyung Wook Park¹, Ju Han Kim¹, Weon Kim¹, Jeong Gwan Cho¹, Jong Chun Park¹, Jung Chaee Kang¹ |
Background: Even with the drug eluting stent, in-stent restenosis (ISR)is still major challenge for the interventional cardiologist. NF-κB transcription factors drive expression of many genes involved in especially inflammation and cell survivival. Previously, we reported that inflammatory reaction is an important role in neointimal formation after coronary stenting in porcine ISR model. Materials and Methods: To test the role of NF-κB in cardiovascular system, we used Ad.dnIKK-β. Neonatal cardiomyocytes (CM) were infected with Ad.EGFP.β-gal or Ad.dnIKK-β for 24 hours prior to activation with TNF-α (50 ng/mL). QRT-PCR was performed to detect the expression of m-RNA of vascular cellular adhesion molecule (VCAM)-1 and intercellular adhesion molecule (ICAM)-1. Apoptotic cell death was determined by ELISA for histone-associated DNA fragments. Results: Pretreatment with TNF-α (3 hours) induced NF-κB depedent pro-inflammatory cytokines of VCAM and ICAM. dnIKK-β reduced TNF-α induced NF-κB translocation and IκB-α degradation, and inhibited the induction of mRNA for VCAM-1 and ICAM-1 by 90±11% (p<0.05) and 80±13% (p<0.05), respectively by QRT-PCR. Ad.dnIKK-β infected CM exhibited increased fragmented DNA compared with normal condition when they were TNF-α pretreated (p<0.01 in MOI 40, p<0.001 in MOI 80) by Cell Death ELISA. Conclusion: Our results suggest that NF-κB inhibitor using dnIKK-β could prevent in-stent restenosis via a mechanism of suppression of inflammatory reaction and induction of apoptosis of proliferative smooth muscle cell.
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