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.
Original language | English (US) |
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Pages (from-to) | 169-175 |
Number of pages | 7 |
Journal | Journal of Surgical Research |
Volume | 175 |
Issue number | 1 |
DOIs | |
State | Published - Jun 1 2012 |
Externally published | Yes |
Keywords
- adeno-associated virus
- gene therapy
- intimal hyperplasia
- restenosis
- vascular smooth muscle cells
- vector
ASJC Scopus subject areas
- Surgery