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 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.
ObjectiveTo observe the effects of endovascular radiation (ER) on the proliferation and apoptosis of medial smooth muscle cells (SMC) and to discuss the possible mechanisms of radiation in the prevention of vascular restenosis (RS) in rabbits after carotid endarterectomy (CEA).MethodsForty rabbits undergoing CEA were randomly divided into four groups (each group=10) and given a radiation dose of 0, 10, 20 and 40 Gy 32P respectively. Rabbits were killed on the 3rd, 7th, 14th, 28th and 56th day after operation. The specimens were collected and histopathologic examinations were done.ResultsProliferation apparently occurred in the intima and media of carotid the lumen became narrow in the control group on the 14 th, 28 th and 56 th day after operation. While in the radiation groups, proliferation was apparently suppressed and the lumen was much less narrowed (P＜0.05). The apoptosis rate of SMCs and PCNA positive cells increased on the 3rd day after operation and reached the peak on the 7th day. There was statistical difference between the ER groups and control group (P＜0.01). The effects were much more evident in 20 Gy and 40 Gy groups compared with 10 Gy group (P＜0.01).ConclusionER may prevent RS by suppressing SMC proliferation and migration as well as inducing SMC apoptosis. The effects are positively correlated with radiation doses. SMC proliferation and apoptosis occur in the early period after balloon injury, while hyperplasia of intima and medial happens later.
【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.
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.
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.
Objective To observe the inhibitory effects of local co-transfection of tissuetype plasminogen activator(tPA) gene and proliferating cell nuclear antigen antisense oligodeoxynucleotides(PCNA-ASODN) on the intima proliferation and restenosis of autograft artery in rabbits. Methods One hundred and twenty male Zelanian rabbits were randomly divided into four groups(n=30, in each group): control group, PCNA-ASODN group, tPA group and tPA+PCNAASODN group. The left and right external iliac arteries (length 1.0 cm) were transplanted reciprocally. The transplanted arteries were respectively soaked in lipofection, PCNAASODN, pBudCE4.1/tPA and pBudCE4.1/tPA+PCNA-ASODN solution about 15 minutes. The transplanted arteries were sutured with 9-0 sutures soaked in PCNA-ASODN and pBudCE4.1/tPA solution. Each group were divided into five subgroups(n=6, in each subgroup) according to the sacrifice time (3 d, 7 d, 14 d, 28 d and 56 d after operation). On every sacrifice time point, the vascular specimens were harvested. The thrombocyte assembling and thrombus forming lining vessel wall were observed by scanning electron microscope. The pathological morphology of transplanted arteries were observed under microscope(HE). The intimal areas and stenosis ratio(%) of transplanted arteries were calculate and analyzed statistically among groups by computer system. The mRNA expression of tPA gene in transplanted ressel wall was detected with vevere transcriptionPCR(RT-PCR). The number of PCNA positive cells in transplanted vessel wall was counted by SP immunochemisty.Results The mRNA expression of tPA gene in the transplanted vessel wall in tPA and tPA+PCNA-ASODN groups was higher than that of the other two groups(P＜0.01).The number of PCNA positive cells in the transplanted arteries in PCNAASODN, tPA and tPA+PCNAASODN groups were significantly lower than that of control group(P＜0.05，P＜0.01). The intimal areas and degrees of luminal stenosis of PCNAASODN, tPA and tPA+PCNAASODN groups were lower than those of control group(P＜0.05，P＜0.01), and those of tPA＋ PCNA-ASODN group were lower than those of PCNA-ASODN and tPA groups(P＜0.05). Scanning electron microscopy showed that there were a few thrombocytes lining the vessel wall of tPA group and tPA+PCNAASODN group and no thrombus, whereas there were abundant thrombocytes and thrombi lining the vessel wall of the control group. Conclusion Co-transfection of tPA gene and PCNA-ASODN can effectively inhibit the proliferation of VSMC, hyperplasia of intima and restenosis of transplanted artery.
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.
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.