Relation Between VEGF And Vascular Positive Remodeling After Stent-implantation And The Effect On The Expression Of VEGF And MAC By Different Stents

Background:Percutaneous coronary intervention (PCI) has become a common treatment of coronary artery diseases. The adverse effects brought with PCI, such as stent restenosis, stent thrombus, late stent malapposition (LSM) and coronary artery aneurysm (CAA), are arousing great attention. The mechanism of LSM and CAA still remains unknown due to the low incidence. Previous studies demonstrated that vascular positive remodeling (VPR) played an important role in the formation of LSM and CAA. Vascular Endothelial Growth Factor (VEGF), which is the only specific mitogenic factor for vascular endothelial cells, is reported to be participated in many vascular remodeling in vascular diseases and tumors. But whether VEGF is also involved in the vascular remodeling after PCI is not clear.Objective:The aim of this study is to investigate the role of VEGF in vascular positive remodeling after stent-implantation. And differences of the expression of VEGF and macrophage antibody (MAC) between different types of stent-implantation are also analyzed to investigate the effect of different stents in the process of vascular positive remodeling.Method:60 healthy New Zealand rabbits were fed with high fat diet and endured balloon injury in both iliac arteries in order to achieve the atherosclerosis model. They were randomly divided into 4 groups and were implanted with base metal stents (BMS), durable polymer sirolimus eluting stents (DPS), biodegradable polymer sirolimus eluting stents (BDS) and polymer-free sirolimus eluting stents (PFS) in either iliac artery. We studied the intravenous ultrasound (IVUS) at 3 different time points (before stent-implantation, instant after stent-implantation and 8 weeks after stent-implantation) and analysis whether there was vascular positive remodeling. The animals were sacrificed 8 weeks after stent-implantation to obtained iliac artery tissues, the morphologic changes and expressions of VEGF and MAC were observed. Result:1) Vascular positive remodeling (VPR) was found in 17 vessel segments among all 53 segments at 8 weeks after stent-implantation. Vessel segments with VPR showed increased expression of VEGF compared with those with NVPR(VPR: 28.53±6.66%; NVPR:19.74±3.57%; P<0.05). And this variance existed in all groups(BMS:27.75±10.74% vs.17.81±2.01%, DPS:40.25±2.77% vs. 20.62±4.28%, BDS:35.04±3.52% vs.21.20±4.14%, PFS:19.66±4.07% vs. 16.25±1.72%; P<0.05). There was a positive correlation between the expression of VEGF and the△EEM-CSA (the difference between EEM-CSA of instant after stent-implanatation and 8 weeks later)2) The incidence of VPR among different stents in our study was BMS 25%, DES 34.15%(DPS 42.86%, BDS 30.77%, PFS 28.57%), including 2 cases of late stent malapposition occurred with DPS and BDS respectively. Incidences of VPR among these 4 groups were no statistical difference (P>0.05). However, significant increased△EEM-CSA were observed in Group DPS and Group BDS(DPS:0.86±0.38mm2, BDS:0.67±0.41mm2, P<0.05) but no statistical differences were observed between these two groups or between Group BMS and Group PFS (BMS:-0.51±0.54mm2, PFS:0.05±0.27mm2, P>0.05).△EEM-CSA in Group DPS-VPR and Group BDS-VPR were still apparently increased (DPS-VPR: 2.47±0.35mm2, BDS-VPR:2.59±0.37mm2, P<0.05), while no statistical differences were observed between Group DPS-VPR and Group BDS-VPR or between Group BMS-VPR and Group PFS-VPR (BMS-VPR:0.96±0.45mm2, PFS-VPR: 1.63±0.24mm2, P>0.05).3) The expression of VEGF in Group DPS and Group BDS (DPS:30.45±9.57%, BDS: 25.74±5.35) were higher than Group BMS (21.11±4.32%) and Group PFS (19.66±4.07%) (P<0.05), and no statistical differences were noted between Group BMS and Group PFS or between Group DPS and Group BDS(P>0.05). Among all the vessel segments with VPR, VEGF expression was increased in Group DPS-VPR and Group BDS-VPR (DPS-VPR:40.25±2.77%, BDS-VPR:35.04±3.52%) (P<0.05), statistical differences were observed between Group DPS-VPR and Group BDS-VPR but not between Group BMS-VPR and Group PFS-VPR (BMS-VPR:27.75±10.74%, PFS-VPR 19.66±4.07%) (P>0.05).4) The expression of MAC was apparently weaker in Group PFS (18.99±2.45%) than other groups(P<0.05), and statistical difference was also noted between Group DPS (44.21±9.01%) and Group BDS (25.49±2.03%), but not noted between Group BMS (35.30±7.79%) with Group DPS or with Group BDS (P>0.05). All groups of the vessel segment with VPR both expressed higher MAC than those with NVPR but there were no statistical differences (P>0.05).Conclusion:1) Expression of VEGF which significantly increased on the vessel segments with VPR, was positively correlated with△EEM-CSA. The result implied the role of VEGF in the vascular remodeling process.2) Enhanced△EEM-CSA and higher expression of VEGF and MAC were observed in Group DPS and Group BDS. Incidence of VPR may increase with these those types of stents due to the polymers which cause apparent inflammation and increase the expression of VEGF.