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.
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.
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 evaluate the effect of low power red laser illumination on the intimal proliferative response in vein graft models.MethodsAutogenous vein graft models were established in 80 rats by transplanting jugular vein to carotid artery by end to end anastomosis, and were randomized into two groups: control group (graft nonilluminated), laser illumination group (0.9 J/cm2).The grafted veins were harvested at 3,7,14 or 28 day respectively after operation. IH (intimal hyperplasia) and SMC (smooth muscle cell) proliferations were pathologically and immunohistochemically observed and analyzed by computer digitizing system. ResultsThere were no significant differences in the intimal average thickness and the areas of lumen between two groups for 3 day. Laser group was significantly lower than the control in both the intimal average thickness and the stenosis of lumen at 7 day,14 day and 28 day (P＜0.05).Immunohistochemical analysis of PCNA indicate the decreased positive cell in laser group compared with the control group (P＜0.01).ConclusionThese preliminary results demonstrate that a certain density of low power red laser illumination in vein graft inhibits SMC proliferation and neointimal hyperplasia in rat.
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.
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.
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 irradiating effect of low intensive microwave (LIM) on pathological process of blood vessel restenosis(RS) and assess the probability of LIM irradiation to prevent was used RS.Methods Fortyfour male healthy New Zealand rabbits were randomly divided into 2 groups. Fogarty catheter traumatize to the tunica intima of iliac artery so as to establish RS models. Two thousand four hundred and fifty MHz microwave with different power of 2 ,5 and 10 mW/cm2 was used, locally to irradiate EIA in irradiating group (1 h/d). Specimens were obtained at different time of 3,7,14 and 28 d after operation. Morphological changes of tissues were observed with HE and EF staining and the area of tunica intima, tunica media and the rate of cavity stenosis were analyzed with image analysis system; apoptosis was detected with TUNEL; phenotype and microstructure of VSMC were observed with TEM. Results After microwave irradiating, inflammatory reaction in early period was suppressed, mural thrombus decreased, the proliferation and migration of VSMC depressed, the area of tunica intima and the rate of cavity stenosis obviously reduced comparing with the control group (P＜0.01). The rate of apoptosis cells showed that there were no obvious differences among each group on 3 d after operation (Pgt;0.05). At other different time, however, the rate of apoptosis cells in irradiating groups obviously increased than that of the control group (P＜0.01), particularly in the one with power of 5 mW/cm2 .The number of synthesis form VSMC in the control group occupied (93.50±3.45)% of the total number of VSMC on 14 d after operation. Most of VSMC appear contractile in irradiating group in which a lot of morphological changes of apoptosis in fibroblast and VSMC existed.Conclusion LIM irradiation could obviously prevented from pathologic procedure of RS. After LIM irradiating, inflammatory reaction in early period is suppressed, the proliferation and migration of VSMC depressed. LIM irradiation promotes cell apoptosis, effectively prohibites the occurring and development of RS. LIM irradiation has had relationship between quantity and effect, power span to effectively prohibit RS, particularly in the one with power of 5 mW/cm2.
