Increased expression of nuclear NF-kappaB after coronary artery balloon injury can be inhibited by intracoronary beta-irradiation.
OBJECTIVE
Molecular mechanisms by which balloon angioplasty injury-induced neointimal hyperplasia can be reduced by intravascular brachytherapy are unclear. We investigated the role of nuclear factor-kappaB (NF-kappaB) in neointimal hyperplasia following intracoronary irradiation.


METHODS
Fifty-four coronary arteries from 30 pigs were divided into 6 groups: sham control, balloon angioplasty injury alone, beta-irradiation at doses of 14 or 20 Gy, and 14 or 20 Gy beta-irradiation immediately followed by balloon injury. Coronary arteries were injured by overstretch balloon angioplasty and then the arteries were irradiated using a Rhenium-188 ((188)Re) beta-emitting solution-filled balloon. Pigs were scarified one day or one week after coronary interventions for molecular detection and six weeks after the procedures for histological examination.


RESULTS
Six weeks after coronary interventions, the histological results show that balloon angioplasty injury had induced intimal hyperplasia in coronary artery but the response was significantly reduced by 28% and 60% when the injury was immediately treated by 14 and 20 Gy (188)Re beta-irradiation, respectively. The expression of arterial NF-kappaB p65, intercellular adhesion molecule-1 (ICAM-1), and vascular cell adhesion molecule-1 (VCAM-1) were detected at one day and one week after the procedures. The treatment of balloon injury could significantly induce the NF-kappaB p65 expression in both gene and protein levels, and such induction could be significantly reduced by (188)Re beta-irradiation at dose of 20 Gy. However, the similar result on the regulation of gene expression affected by the beta-irradiation could not be observed in ICAM-1 and VCAM-1.


CONCLUSIONS
The inhibitory effect of intracoronary brachytherapy on neointimal formation following overstretch balloon angioplasty could involve inhibition of NF-kappaB p65.
Su
Chun-Hui
CH
Department Biological Science and Technology, National Chiao Tung University, Hsinchu, Taiwan.
Hsieh
Bor-Tsung
BT
Leung
Stephen-Wan
SW
Wu
Chiung-Jen
CJ
Chiu
Sheng-Yi
SY
Lin
Chih-Sheng
CS
D000818:Animals; D001610:Beta Particles / Q000627:therapeutic use*; D001918:Brachytherapy / Q000379:methods*; D002404:Catheterization / Q000009:adverse effects* / Q000379:methods; D003327:Coronary Disease / Q000473:pathology / Q000517:prevention & control / Q000532:radiotherapy*; D003331:Coronary Vessels / Q000293:injuries / Q000528:radiation effects*; D004307:Dose-Response Relationship, Radiation; D005786:Gene Expression Regulation; D006965:Hyperplasia / Q000473:pathology / Q000517:prevention & control / Q000532:radiotherapy; D018799:Intercellular Adhesion Molecule-1 / Q000235:genetics / Q000378:metabolism; D016328:NF-kappa B / Q000235:genetics / Q000378:metabolism*; D013552:Swine; D013997:Time Factors; D017539:Tunica Intima / Q000293:injuries / Q000528:radiation effects*; D019010:Vascular Cell Adhesion Molecule-1 / Q000235:genetics / Q000378:metabolism
D016328:NF-kappa B; D019010:Vascular Cell Adhesion Molecule-1; D018799:Intercellular Adhesion Molecule-1