Abstract
BACKGROUND: Gene therapy has attracted attention for its potential to treat several cardiovascular diseases. The use of adeno-associated viral (AAV) vectors to facilitate therapeutic gene transfer to suppress intimal hyperplasia is a promising concept. The objective of this study was to analyze the in vivo transduction of a novel recombinant AAV-2/9 vector with SM22α promoter, containing β-galactosidase gene (LacZ) or green fluorescent protein (GFP) as reporter genes, to the medial layer smooth muscle cells (SMCs) of swine coronary and peripheral arteries. METHODS: The AAV-2/9 vector containing SM22α (1 × 10(13) pfu) were administered into carotid/femoral/coronary arteries of domestic swine using irrigating balloon catheter-based gene delivery. Following gene transfer, cryosections of arteries were processed for X-Gal and GFP analysis. Fluorescence microscopy and Western blotting were done to analyze the GFP expression in the SMCs. RESULTS: LacZ mRNA expression was visualized in the medial layer 7 d after vector administration. The GFP expression was detected at day 7 and lasted for at least 2 mo showing the longer-lasting expression of the AAV-2/9 vector. Control arteries did not show any expression of GFP or LacZ. There was no significant effect of AAV-2/9 viral transduction on serum amylase, fibrinogen, and serum CRP levels. CONCLUSION: These finding support the use of AAV-2/9 as a vector to effectively transduce a gene in SMCs of coronary and peripheral arteries without causing inflammation.