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.
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 domesticswine 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.
Authors: Katri Pajusola; Marcin Gruchala; Hana Joch; Thomas F Lüscher; Seppo Ylä-Herttuala; Hansruedi Büeler Journal: J Virol Date: 2002-11 Impact factor: 5.103
Authors: Y Maeda; U Ikeda; Y Ogasawara; M Urabe; T Takizawa; T Saito; P Colosi; G Kurtzman; K Shimada; K Ozawa Journal: Cardiovasc Res Date: 1997-09 Impact factor: 10.787
Authors: Oliver J Müller; Barbara Leuchs; Sven T Pleger; Dirk Grimm; Wolfgang-M Franz; Hugo A Katus; Jürgen A Kleinschmidt Journal: Cardiovasc Res Date: 2006-01-31 Impact factor: 10.787
Authors: Anne-Kathrin Zaiss; Qiang Liu; Gloria P Bowen; Norman C W Wong; Jeffrey S Bartlett; Daniel A Muruve Journal: J Virol Date: 2002-05 Impact factor: 5.103
Authors: Kevin W Southerland; Sarah B Frazier; Dawn E Bowles; Carmelo A Milano; Christopher D Kontos Journal: Transl Res Date: 2012-12-27 Impact factor: 7.012
Authors: Terence R Flotte; Eric Daniels; Janet Benson; Jeneé M Bevett-Rose; Kenneth Cornetta; Margaret Diggins; Julie Johnston; Susan Sepelak; Johannes C M van der Loo; James M Wilson; Cheryl L McDonald Journal: Hum Gene Ther Clin Dev Date: 2017-11-27 Impact factor: 5.032
Authors: I Fishbein; D T Guerrero; I S Alferiev; J B Foster; N G Minutolo; M Chorny; A M Monteys; K H Driesbaugh; C Nagaswami; R J Levy Journal: Gene Ther Date: 2017-08-23 Impact factor: 5.250
Authors: Markus Vogt; Benjamin Schulz; Ahmed Wagdi; Jan Lebert; Gijsbert J van Belle; Jan Christoph; Tobias Bruegmann; Robert Patejdl Journal: Theranostics Date: 2021-03-20 Impact factor: 11.556
Authors: Bahman Hooshdaran; Benjamin B Pressly; Ivan S Alferiev; Jonathan D Smith; Philip W Zoltick; Cory M Tschabrunn; Robert L Wilensky; Robert C Gorman; Robert J Levy; Ilia Fishbein Journal: Sci Rep Date: 2022-03-31 Impact factor: 4.996