Purpose: 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.
Materials and 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.
Conclusion: The inhibitory effect of intracoronary brachytherapy on neointimal formation following overstretch balloon angioplasty could involve inhibition of NF-kappaB p65.