ABSTRACT
Objective To study the effect of Pioglitazone(PIO) on intimal hyperplasia after vein graft and its potential mechanism.Methods 32 male Sprague-Dawley rats were randomly divieded into two groups,one admisnistrated with PIO(3 mg· kg-1 · d-1) and the other with saline.A week later,the right common carotid arteries were reconstructed using homolateral external jugular veins in rats.The drugs treatment was continued after surgery for 2 or 4 weeks until grafted veins were harvested.The neointima thickness was measured by Computer image analysis software.To observe the activation of ERK1/2 pathway,the western blot were performed.In vitro,human great saphenous vein smooth muscle cells were co-cultured with PIO,and cells proliferation was detected by the CCK-8 assay.The TUNEL staining was performed to determine apoptosis.Results PIO treatment significantly attenuated intimal thickening compared with the the control group both at second [(8.56 ± 1.64) μm vs (25.44 ± 0.89) μm,P ＜ 0.01] and fourth week [(10.51 ± 1.47) μm vs (35.69 ± 1.07) μm,P ＜ 0.01)] after veins graft.Also PIO inhibited the ERK1/2 activation in grafted veins.In vitro,PIO significantly reduced PDGF-induced cells proliferation and increased cells apoptosis.Conclusion PIO effectively improved intimal hyperplasia in grafted veins perhaps associated with its ability to suppress vascular smooth muscle cells proliferation and enhance cell apoptosis,and might be related to the down regulation of ERK1/2 activity.
ABSTRACT
Objective To study the effect of rat angiotensin Ⅱ receptor (AT2R) gene transfer mediated by adenoviral vector on neointimal proliferation after rat carotid artery injury. Methods AT2R gene was transducted into the carotid artery by adenoviral vector with GFP after carotid balloon injury. Restenosis models were established in Wistar rats. Immunostaining was performed to examin the expression of AT2R in local arteries. Neointima/media area ratio at day 21 after gene transfer was measured by morphometric analysis. Results The transduction rate of AT2R gene in rat carotid arteries was 40% and the gene expressed constantly in the vessel walls. Neointima/media area ratio of the gene transduction group was significantly reduced (48%) compared with the control group at day 21 after gene transfer. Conclusion The results suggest the possibility that AT2R gene transfer can inhibit proliferation of arterial intima after balloon injury and it is a potential therapeutic approach to prevent neointimal hyperplasia.