Objective To evaluate the efficacy and safety of drug-eluting stents in treating patients with coronary artery disease compared with bare metal stents. Methods MEDLINE, EMBASE, CBMdisc and other databases of clinical trials were searched for meta-analysis and randomized controlled trials (RCTs) both in Chinese and English language. Conference abstracts, personal reference lists, reference lists of retrieved studies and some websites were also searched. Statistical analysis was performed using RevMan 4.2 software. Results Meta-analysis was performed on the results of 25 RCTs with 5 different drug-eluting stents. Seven trials evaluated efficacy and safety of sirolimus-eluting stent, the results of meta-analysis indicated that SES decreased rates in stent restenosis compared with bare metal stent, and therefore the target lesion revascularization and adverse cardiac event rates, no “catch up” were found. Eight trials compared a paclitaxel-eluting stent with bare metal stent, similar results were found, i.e. decreased stent restenosis rate, target lesion revascularization and adverse cardiac event rates in patients receiving paclitaxel-eluting stent compared with bare metal stent. Three trials compared CYPHERTM and TAXUS stents head to head, and the combined analysis showed a superiority of CYPHERTM to TAXUS. But available data can not draw a conclusion with regard to the effect of drug-eluting stents on mortality, occurrence of MI or stent thrombosis. Everolimus-eluting stent had the same performance as these two drug-eluting stents above, but because of a small sample size, no further conclusion can be made. Actinomycin D eluting stents and 7-hexanoyltaxol-eluting stents increased restenosis rate and stent thrombosis rate respectively. Poor performance limited further clinical trials of these two stents. Conclusions Sirolimus-eluting stent and polymetric paclitaxel-eluting stent are efficient and safe in patients with coronary artery atherosclerosis. Sirolimus eluting stent CYPHERTM seems better than paclitaxel eluting stent TAXUS.
ObjectiveTo discuss the role of nuclear factor-kappa B in restenosis after angioplasty.MethodsRelated literatures of recent 5 years were reviewed.ResultsNuclear factor-kappa B could lead to hyperplasia of vascular intima which resulted from proliferation and decrease of apoptosis of vascular smooth muscle cells.ConclusionNuclear factor-kappa B plays an important role in restenosis after angioplasty.
Abstract: Coronary artery bypass grafting (CABG) is one of the conventional treatments of coronary artery disease. Though the artery grafts have its own superiority, autologous great saphenous vein is still commonly used. Ten years after operation, half of the vein grafts will be occluded and half of the remainder will often undergo severe pathological conditions. The poor long term patency of vein grafts has become the bottleneck of the efficiency of CABG. The restenosis of vein grafts resulting from neointima and atherosclerosis has become an urgent problem waiting to be resolved. As the study on the molecular mechanism and pathophysiology of the vein grafts disease develops, many therapeutic schedules have been made, including drug therapy, external stent, expanding solution and gene therapy. By contrast, gene therapy has a broader prospect. This article will have a review on the prevention of restenosis of the vein grafts after CABG.
ObjectiveTo investigate the effectiveness of epidermal growth factor receptor antagonist (AG-1478) on chronic proliferative cholangitis (CPC), so as to investigate new treatment approach for hepatolithiasis associated with CPC. MethodsForty-six SD rats were divided into 5 groups: CPC model group (n=10), only made models. AG-1478 treatment group (divided into 3 mg/kg， 6 mg/kg， and 12 mg/kg groups, n=10 per group), the common bile ducts in CPC animal model received an intralumenal administration of AG-1478 at the meantime of modeling, followed by intraperitoneal AG-1478 injection of 1.5 mg/(kg·d) for 7 days. Sham operation group (SO group, n=6). Subsequently, histopathological observation, immunohistochemistry, real time PCR， and Western blot were used to evaluate the mRNA expression and influence of AG-1478 on the hyperplasia （EGFR， ki-67， BrdU， collagen Ⅰ protein） and lithogenic potential (Mucin 5AC) of CPC. ResultsCompared with CPC model group, the expressions of EGFR, ki-67， and BrdU were obviously decreased in the AG-1478 treatment group. Also, the inhibition of hyperplasia of biliary epithelium and collagen fibers were confirmed by histopathological observation. Additionally, the expressions of Mucin 5AC mRNA and collagen Ⅰ protein remarkable decreased in the AG-1478 treatment group (Plt;0.05). Conclusions EGFR inhibitor (AG-1478) could shows inhibitory effectivenss on the CPC-mediated hyperplasia and lithogenic potential, and therefore holds promise as the new treatment approach for CPC.
Objective To study the mechanism of restenosis of the vein graft and the effect of the grafting injury to the vein graft. Methods One side of the 36 healthy rabbits was randomly chosen as the V-A group, and on the side a 1.5cmlong femoral vein was obtained, and an 0.5-cm-long segment of the obtained femoral vein was separated as the control group. The remaining 1-cm-long femoral vein was inverted and was autogenously implanted into the femoral artery on the same side of the rabbit. The other side of the rabbits was chosen as the V-V group, and on this side a 1-cm-long femoral vein was obtained ex vivo and then was sutured in situ. The vein grafts on both sides were harvested 4 weeks after operation. The specimens from the harvested vein grafts were stained with HE and theelastic fiber Victoria blue for an observation on the histological changes in the walls of the vein grafts, and the specimens were also stained by the immunohistochemistry of the proliferating cell nuclear antigen (PCNA) for an observation on the wall cell proliferation of the vein grafts. The changes in the ultrastructure of the proliferated wall cells of the vein grafts were observed under electron microscope. The two sides of the rabbits were compared. Results The smooth muscle cells of the media developed hyperplasia, but theintima and the media remained unchanged in their thickness (3.50±0.41 μm, 12.23±1.59 μm) in the V-V group, with no difference when compared with the control group (3.40±0.37 μm, 12.14±1.62 μm); however, when compared with the V-A group (25.60±3.21 μm, 21.30±2.47 μm),there was a significant difference in the thickness (Plt;0.01). There were no cells positive for PCNA by the immunohistochemistry examination in the control group. The cells positive for PCNA were found in the intima and the media in both the V-V group and the V-A group; however, the percentageof the cells positive for PCNA in the intima and the media was significantly greater in the V-A group than in the V-V group (16.4%±1.9% and 36.5%±3.7% vs 5.9%±1.3% and 23.4%±3.4%, Plt;0.01). In the V-V group, the endothelial cell could be observed under transmis-sion electron microscope, which was flat and had a processlike villus at its free end, and the endothelial cells were closely arranged andhad hyperplasia of the smooth muscle cells in the media. But in the V-A group,the endothelial cells had an obvious hyperplasia with an irregular shape and a widened space between the cells, and in the intima a great amount of the smooth muscle cells could be observed, which had a broken basement membrane. The smooth muscle cells also had an obvious hyperplasia in the media. The shape and alignment of the endothelial cells in the control group were similar to those in the V-V group, but the hyperplasia of the smooth muscle cells was not observed in the media. Conclusion The grafting injury can cause hyperplasia ofthe vascular wall cells, and if the hemodynamics is changed simultaneously, more serious hyperplasia and cell migration can be observed from the media to the intima, resultingin restenosis of the blood vessels. So, if we can reduce the grafting injury and improve the microcirculation of the vein graft, we may find out the methods ofpreventing restenosis of the vein graft. The animal model of the V-V graftcan help to understand the mechanism of restenosis of the vein graft.
Objective To review various kinds of therapeutic methods for restenosis after reconstructive vascular operation. Methods The literatures about prevention and treatment for restenosis after reconstructive vascular operation were reviewed. Results Therapeutic methods for vascular restenosis include gene therapy, drug treatment, placing external stent around the vein graft and physical therapy. The methods of gene therapy include transferring genes that inhibit the proliferation of vascular smooth muscle cell (VSMC) and inactivating genes that promote the proliferation of VSMC through technology of antisensenucleic acids or RNA interference. Conclusion Current treatment for restenosis after reconstructive varscular operation have both advantages and disadvantages, some of which are still being disputed. With the development of the technology of molecular biology, gene therapy would be the most effective therapy method for vascular restenosis.
Objective To observe expression of human antithrombin Ⅲ (hAT-Ⅲ) gene in vascular endotheliallike cells(VELCs) after transfected. Methods Human bone marrow mesenchymal stem cells(BMMSCs) were isolated, cultured and proliferated in vitro, and were differentiated into VELCs. Then, the VELCs were divided into experimental group cells and control group cells randomly. Plasmid DNA with hAT-Ⅲ gene was transfected into VELCs by liposome mediate. At last, the hAT-Ⅲ expression was determined by reverse transcriptpolymerase chain reaction(RT-PCR), immunohistochemical stain(IHCS), Westernblotting and chromogenic substrate assay at 72h and 96h respectively. In the control group, the plasmid DNA was replaced by TE buffer, and the other methods were the same as the experimental group. Results RT-PCR showed that the specific DNA fragment of hAT-Ⅲ could be amplifed in the experimental group cells, none in the control group. IHCS showed positive expression of hAT-Ⅲ in the experimental group cells, negative in the control group. Westernblotting showed that the specific band of hAT-Ⅲ could be detected in the experimental group cells culture fluid, none in the control group. Chromogenic substrate assay showed that the hAT-Ⅲ activity of the experimental group cells was 9.50%±1.52%, the control group was 1.83%±1.17%， there was statistically difference between two groups(t=7.910，Plt;0.01). Conclusion The hAT-Ⅲ gene could be transfected into VELCs and expressed successfully.
Coronary artery bypass grafting (CABG) is a major treatment method for coronary artery disease，but postoperative vein graft restenosis remains an unsolved problem. Research has confirmed that perioperative antiplatelet therapy can effectively reduce early coronary artery bypass graft thrombosis. Lipid-lowering therapy can significantly improve long-term patency of saphenous vein grafts after CABG. In addition，gene therapy provides a new direction to prevent vein graft restenosis after CABG.
Abstract:Objective To evaluate the effect of external stents on preventing vein graft neointima formation and medial thickening with non-restrictive macro porous polyester stent around porcine vein grafts. Methods Studies were performed by using ＂white race＂ pigs （n= 10） weight 25-30 kg. All the animals underwent bilateral saphenous vein into carotid artery bypass grafting. In each animal, a maeroporous stent was placed around a graft on one side and a control （unstented） graft on the opposite side. The polyester stent was shaped to cover both anastomoses completely. The size of the stem allowed unrestricted expansion of the graft in initial response to arterial pressure. After 35 days of surgery,all animals were taken to remove the grafts. Graft wall dimensions, platelet- derived growth factor （PDGF） expression and cell proliferation using proliferating cell nuclear antigen （PCNA） were measured on histological sections. Results Stents significantly reduced neointimal thickening （0. 4872 ± 0. 0706 mm vs. 0. 2259± 0. 0553mm,P〈0. 01）and medial thickening （0. 6246±0. 0859mm vs. 0. 4201±0. 0615mm,P〈0. 01）. Stents significantly reduced the percentage of cells expressing PDGF and PCNA. Media, intimal PCNA index was reduced from 7. 980/00± 4. 060/00 to 3.35±0.95%（P〈0.01）, PDGF index was reduced from 9.47%±5.35% to 2.67%± 0.97% （P 〈0. 01）. Conclusion External non-restrictive polyester stent can significantly inhibit neointimal formation and medial thickening, and may prevent late vein grafts restenosis.
Abstract: Objective To investigate the effect of keeping implanted vein graft from restenosis by local application of paclitaxel. Methods Ninetysix New Zealand rabbits were randomly divided into three groups, control group (n=32), group Ⅰ(n=32), group Ⅱ(n=32). The vein graft stenosis model was made in all rabbits. In group Ⅰand group Ⅱ, 1μg and 8μg of paclitaxel was applied locally in pluronic gelatin respectively. There were no local treatment in control group. Grafts were harvested at 1, 2, 4, and 6 weeks and underwent morphological analysis as well as immunohistochemical analysis. Results The intimal thickness in group Ⅱ were significantly decreased compared to those in control group at 1,2,4, and 6 weeks after operation (30.10±4.50μm vs. 48.20±9.16μm, 40.70±6.91μm vs. 54.20±8.67μm, 54.70±7.11μm vs. 68.60±13.72μm, and 68.70±8.24μm vs. 76.40±12.98μm, Plt;0.05). The CD8 positive cells and metallothionein positive cells in group Ⅰand group Ⅱ were significantly decreased compared to those in control group (Plt;0.05). Conclusion The results suggest that perivascular application of paclitaxel inhibits neointimal hyperplasia of vein grafts in a rabbit model, and paclitaxel may have a therapeutic potential for the treatment of vein graft disease.
