SERCA2a gene transfer prevents intimal proliferation in an organ culture of human internal mammary artery
| Autor: | L Hadri, A‐M. Lompré, Lifan Liang, I Limon, P. Le Prince, Roger J. Hajjar, Stephanie Lehoux, Fabrice Atassi, M Glorian, Larissa Lipskaia, Bruno Esposito |
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| Přispěvatelé: | Contrôle du Phénotype des Cellules Musculaires Lisses (CPCML), Adaptation Biologique et Vieillissement = Biological Adaptation and Ageing (B2A), Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut de Biologie Paris Seine (IBPS), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut de Biologie Paris Seine (IBPS), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), AHA [SDG 0930116N], NIH [1K01HL103176, R01 HL078691, HL057263, HL071763, HL080498, HL083156], Leducq Foundation through the Caerus network [05 CVD 03], Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut de Biologie Paris Seine (IBPS), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut de Biologie Paris Seine (IBPS), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut de Biologie Paris Seine (IBPS), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS) |
| Jazyk: | angličtina |
| Rok vydání: | 2013 |
| Předmět: |
Gene isoform
medicine.medical_specialty Pathology Vascular smooth muscle Intimal hyperplasia [SDV.BC]Life Sciences [q-bio]/Cellular Biology 030204 cardiovascular system & hematology Biology In Vitro Techniques Organ culture Article Muscle Smooth Vascular Sarcoplasmic Reticulum Calcium-Transporting ATPases Coronary Restenosis 03 medical and health sciences restenosis 0302 clinical medicine Restenosis Internal medicine Genetics medicine Humans Calcium Signaling Mammary Arteries gene transfer Molecular Biology 030304 developmental biology Cell Proliferation 0303 health sciences Endoplasmic reticulum Gene Transfer Techniques Genetic Therapy medicine.disease 3. Good health internal mammary artery Cardiology cardiovascular system Molecular Medicine Calcium Tunica Intima SERCA2a Perfusion Ex vivo |
| Zdroj: | Gene Therapy Gene Therapy, Nature Publishing Group, 2013, 20 (4), pp.396-406. ⟨10.1038/gt.2012.50⟩ Gene therapy Gene Therapy, 2013, 20 (4), pp.396-406. ⟨10.1038/gt.2012.50⟩ |
| ISSN: | 0969-7128 1476-5462 |
| DOI: | 10.1038/gt.2012.50⟩ |
| Popis: | International audience; Coronary restenosis, a major complication of percutaneous balloon angioplasty, results from neointimal proliferation of vascular smooth muscle cells (VSMCs). The sarco/endoplasmic reticulum calcium ATPase 2a isoform (SERCA2a), specific to contractile VSMCs, has been reported previously to be involved in the control of the Ca2+-signaling pathways governing proliferation and migration. Moreover, SERCA2a gene transfer was reported to inhibit in vitro VSMC proliferation and to prevent neointimal thickening in a rat carotid injury model. The aim of this study was to evaluate the potential therapeutic interest of SERCA2a gene transfer for prevention of in-stent restenosis using a ex vivo model of human left internal mammary artery (hIMA) intimal thickening. Left hIMAs, obtained at the time of aorto-coronary bypass surgeries, were subjected to balloon dilatation followed by infection for 30 min with adenoviruses encoding either human SERCA2 and green fluorescence protein (GFP) or control gene (beta-galactosidase, beta-gal) and GFP. Proliferation of subendothelial VSMCs and neointimal thickening were observed in balloon-injured hIMA maintained 14 days in organ culture under constant pressure and perfusion. SERCA2a gene transfer prevented vascular remodeling and significantly (P < 0.01, n = 5) reduced neointimal thickening in injured arteries (intima/media ratio was 0.07 +/- 0.01 vs 0.40 +/- 0.03 in beta-gal-infected arteries). These findings could have potential implications for treatment of pathological in-stent restenosis. Gene Therapy (2013) 20, 396-406; doi: 10.1038/gt.2012.50; published online 5 July 2012 |
| Databáze: | OpenAIRE |
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