【Abstract】 Objective To reduce restenosis in vein grafts after coronary artery bypass grafting, to investigate theeffect of human tissue factor pathway inhibitor(TFPI) gene del ivery on neointima formation. Methods The eukaryotic expressed plasmid vector pCMV-(Kozak) TFPI was constructed. Forty-eight Japanese white rabbits were randomly divided into 3 groups with 16 rabbits in each group: TFPI group, empty plasmid control group and empty control group. Animal model of common carotid artery bypass grafting was constructed. Before anastomosis, vein endothel iocytes were transfected with cationic l iposome containing the plasmid pCMV- (Kozak) TFPI (400 μg) by pressurizing infusion (30 min) in TFPI group. In empty plasmid control group, vector pCMV- (Kozak) TFPI was replaced by empty plasmid pCMV (400 μg). In empty control group, those endothel iocytes were not interfered. After operation, vein grafts were harvested at 3 days for immunohistochemical, RTPCR and Western-blot analyses of exogenous gene expression and at 30 days for histopathology measurement of intimal areas, media areas and calculation of intimal/media areas ratio. Luminal diameter and vessel wall thickness were also measured byvessel Doppler ultrasonography and cellular category of neointima was analyzed by transmission electron microscope at 30 days after operation. Results Human TFPI mRNA and protein were detected in TFPI group. The mean luminal diameter of the TFPI group, empty plasmid control group and empty control group was (2.68 ± 0.32) mm, (2.41 ± 0.23) mm and (2.38 ± 0.21) mm respectively. There were statistically significant differences between TFPI group and control groups (P lt; 0.05). The vessel wall thickness of the TFPI group, empty plasmid control group and empty control group was (1.09 ± 0.11) mm, (1.28 ± 0.16) mm and (1.34 ± 0.14) mm respectively. There were statistically significant differences between TFPI group and other control groups (P lt; 0.01). The mean intimal areas, the ratio of the intimal/media areas of the TFPI group were (0.62 ± 0.05) mm2and 0.51 ± 0.08 respectively, which were reduced compared with those of the two control groups(P lt; 0.05). The mean media areas had no significant differences among three groups (P gt; 0.05). Through transmission electron microscope analyses, no smoothmuscle cells were seen in neointima of TFPI group in many visual fields, but smooth muscle cells were found in neointima of two control groups. Conclusion Human TFPI gene transfection reduced intimal thickness in vein grafts.
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.
ObjectiveTo investigate the risk factor for restenosis of esophageal anastomosis stricture after esophageal cancer operation.
MethodsWe retrospectively analyzed the clinical data of 83 patients including 61males and 22 females at age of 58.9(41-81) years with esophageal anastomoic stricture after esophageal cancer operation between January 2002 and December 2013. According to whether the patients developed to restenosis or not, the statistical test and logistic regression was conducted to analyze the risk factors for restenosis.
ResultsIn the 83 patients with esophageal anastomoic stricture after esophageal cancer surgery, 35 patients (42.2%) experienced restenosis within the following-up of 1 year. The result of logistic regression analysis indicated that restenosis appeared in 3 months (Wald value=23.3, P < 0.001), the interval between two subsequent sessions of more than 4 weeks at each esophagus dilatation(Wald value=4.8, P=0.029) and the stricture diameter of less than 12 mm after dilation (Wald value=5.8, P=0.016) are the independent risk factors for restenosis in esophageal anastomotic stricture.
ConclusionFor the patients with esophageal anastomoic stricture after esophageal cancer operation, we believe that it's conducive to reduce esophageal restenosis if the interval between dilations is within 4 weeks and the diameter of stricture after dilation can reach above 12 mm.
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 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.
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.
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.
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 find out the follow-up results of early in-stent restenosis (ISRS) and develop effective way to improve clinical treatment and precaution of restenosis. Methods The data from a registry of 51 consecutive patients who underwent elective carotid artery angioplasty and stenting （CAS） at our institution between Jan. 2003 and Sept. 2005 were retrospectively reviewed. Complete data for 37 of these patients were available. All patients underwent duplex ultrasound scanning in follow-up period, which was used to determine the degree of restenosis. Results CAS was performed in 37 patients， 8.1% (3/37) were women. Mean age was (70.5±5.9) years. Mean time of follow-up was (12.2±7.7) months. Sixteen (43.2%) caces of ISRS （gt;30%） were found by color duplex ultrasound scanning， but only 1 (2.7%) ISRS was found gt;50%; 3 female patients had minor ISRS. Among all factors, female patients had higher incidence of ISRS than male (P=0.038); balloon-expanding after stenting and accompanying with other artherosclerosis of periphery vessel had correlation about ISRS （P=0.037, P=0.016）. Conclusion The severe restenosis rate is acceptable. Female patients were more likely to have ISRS. Balloon-expanding maybe have effect on reducing incidence of ISRS and controlling artherosclerosis was helpful.
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.
