ABSTRACT
<p><b>OBJECTIVE</b>To investigate the effect of phVEGF165 transfer on vascular remodelling after balloon injury and its possible mechanisms.</p><p><b>METHODS</b>90 New Zealand white rabbits were divided randomly into 3 groups: group I (balloon injury group), group II (pAdtrackCMV group) and group III (pAdtrackCMV-VEGF165 group). All animals were given hypercholesterol diet for 7 days before experiment and continued to receive hypercholesterol diet until being killed. Each group was further divided into five subgroups according to the sacrifice time (3 days, 1, 2, 4 and 8 weeks after transfection). Blood samples and arteries were harvested for further analysis.</p><p><b>RESULTS</b>At the end of 2 weeks, areas of neointima plus media of group III were smaller than those of group I and II (P < 0.05). The areas under external elastic membrane were larger in group III at 4 weeks and lumen stenosis rates were significantly lower than group I and II (P < 0.05 or 0.01). In group III, VEGF165, metalloproteinases (MMPs) -1, -2, -9 and their tissue inhibitors (TIMPs) 1, 2 could be detected from 3 days after gene transfer and reached the highest level at 2 weeks time and could not be detected by 8 weeks time. In groups I and II, MMP-2 and TIMP-1, -2 could be detected during the whole procedure and the value of TIMP1/MMP1 was significantly higher than in group III (P < 0.01).</p><p><b>CONCLUSION</b>Remodelling is the main reason for restenosis (RS) after vascular balloon injury. Local pAdtrackCMV-VEGF165 transfer can specifically change the expression of MMPs and facilitate the positive remodelling process, hence, inhibiting restenosis.</p>
Subject(s)
Animals , Male , Rabbits , Angioplasty, Balloon , Coronary Restenosis , Pathology , Endothelial Growth Factors , Genetics , Physiology , Intercellular Signaling Peptides and Proteins , Genetics , Physiology , Lymphokines , Genetics , Physiology , Matrix Metalloproteinases , Metabolism , Vascular Endothelial Growth Factor A , Vascular Endothelial Growth FactorsABSTRACT
AIM: To investigate the effect of VEGF gene transfer on matrix metalloproteinases(MMPs) and tissue inhibitor of metalloproteinases(TIMPs) expression after vascular balloon injury. METHODS: 90 New Zealand white rabbits were divided into 3 groups randomly: group Ⅰ(balloon injury group), groupⅡ (pAdtrackCMV group) and group Ⅲ(pAdtrackCMV-VEGF165 group). Hypercholesterol diet was given for 7 days before experiment and continued to receive until the animals were killed. Each group were divided into five subgroups according to the sacrifice time. Blood samples and iliac arteries were harvested for further analysis. RESULTS: In group Ⅰ and Ⅱ, MMP2 and TIMP1,2 expressions were detected during the whole process ,while in group III ,MMP1,2,9 and TIMP1,2 could be detected from 3 days after gene transfer and reached the highest level at 1 week and could not be detected at 8 week. CONCLUSIONS: Imbalance expression of MMPs and TIMPs occurred after vascular injury and this may be the reason of pathological remodeling. Local phAdtrackCMV-VEGF165 transfer could specifically change the expression of MMPs and facilitate the positive remodeling process after vascular injury.