1. ¹Department of Geriatric Medicine, Osaka University Medical School, Suita, Japan
2. ²Division of Gene Therapy Science, Osaka University Medical School, Japan
3. ³Kankyo Bailis, Shiga, Japan

Correspondence: R Morishita, Associate Professor, Division of Gene Therapy Science, Osaka University Medical School, 2-2 Yamada-oka, Suita 565, Japan

The first two authors contributed equally to this work

Received 10 March 2002; Accepted 1 August 2002.

Abstract

Application of DNA technology to regulate the transcription of disease-related genes has important therapeutic potential. The transcription factor NFB plays a pivotal role in the transactivation of inflammatory and adhesion molecule genes, leading to vascular lesion formation. Double-stranded DNA with high affinity for NFB may be introduced as 'decoy' cis elements to bind NFB and block the activation of genes mediating inflammation, resulting in effective drugs for treating intimal hyperplasia. In this study, we tested the feasibility of NFB decoy therapy to treat neointimal formation in a porcine coronary artery balloon injury model as a pre-clinical study.

An angioplasty catheter was introduced into the left anterior descending coronary artery of the pig to cause vascular injury. First, we tested the feasibility of transfection of FITC-labeled NFB decoy ODN using a hydrogel balloon catheter. Fluorescence due to NFB decoy ODN could be detected throughout the medial layer. Therefore, we transfected NFB decoy ODN into the balloon-injured LAD using a hydrogel catheter. Histological evaluation demonstrated that the neointimal area in the balloon-injured artery was significantly reduced by NFB decoy ODN as compared to scrambled decoy ODN at 1 week after single transfection, accompanied by a significant reduction in PCNA-positive stained cells (P<0.01). Interestingly, the reduction of ICAM-positive staining was observed, accompanied by the inhibition of migration of macrophages. Of importance, intravascular ultrasound (IVUS) confirmed that neointimal area in the balloon-injured artery was significantly reduced by NFB decoy ODN at 4 weeks after transfection (P<0.01). Interestingly, the inhibition of neointimal area was only limited to the lesion transfected with NFB decoy ODN, while other lesions without NFB decoy ODN demonstrated a marked increase in neointimal formation.

Here, we report the successful in vivo transfer of NFB decoy ODN using a hydrogel catheter to inhibit vascular lesion formation in balloon-injured porcine coronary artery.