title: SERCA2a gene transfer prevents intimal proliferation in an organ culture of human internal mammary artery.
abstract: 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 Ca(2+)-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 (β-galactosidase, β-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 β-gal-infected arteries). These findings could have potential implications for treatment of pathological in-stent restenosis.
authors: Transatlantic Cardiovascular Research Centre, Mount Sinai School of Medicine, New York, NY 10029-6574, USA. larissa.lipskaia@mssm.edu
authors: L
authors: L
authors: Lipskaia
authors: L
authors: L
authors: Hadri
authors: P
authors: P
authors: Le Prince
authors: B
authors: B
authors: Esposito
authors: F
authors: F
authors: Atassi
authors: L
authors: L
authors: Liang
authors: M
authors: M
authors: Glorian
authors: I
authors: I
authors: Limon
authors: A-M
authors: AM
authors: Lompre
authors: S
authors: S
authors: Lehoux
authors: R J
authors: RJ
authors: Hajjar
mesh_terms: D002118:Calcium / Q000378:metabolism; D020013:Calcium Signaling; D049109:Cell Proliferation; D023903:Coronary Restenosis / Q000517:prevention & control / Q000628:therapy; D018014:Gene Transfer Techniques; D015316:Genetic Therapy; D006801:Humans; D066298:In Vitro Techniques; D008323:Mammary Arteries / Q000473:pathology*; D009131:Muscle, Smooth, Vascular / Q000378:metabolism* / Q000473:pathology; D053498:Sarcoplasmic Reticulum Calcium-Transporting ATPases / Q000235:genetics* / Q000378:metabolism; D017539:Tunica Intima / Q000378:metabolism* / Q000473:pathology
chemical_list: D053498:Sarcoplasmic Reticulum Calcium-Transporting ATPases; C506946:ATP2A2 protein, human; D002118:Calcium