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Aim To explore the role and mechanism of nuclear receptor subfamily 1,group D,member 1(NR1D1)in the proliferation and migration of mouse adventitial fibroblasts(AFs). Methods Primary AFs isolated from C57BL/6J mice were cultured. Adenovirus carrying Nr1d1 gene was used to overexpress NR1D1 in AFs. The expression of β-catenin was restored by SKL2001. Proliferating cell nuclear antigen(Ki-67)immunofluorescence staining and CCK-8 staining were used to determine cell proliferation,and scratch test was used to determine cell migration. qPCR was used to determine the mRNA level of Nr1d1. Western blot was used to determine the protein levels of NR1D1 and β-catenin. To investigate the role of NR1D1 in intimal hyperplasia,20 male wild type C57BL/6J mice were randomly divided into sham group,carotid artery endothelial injury,sham+SR9009(NR1D1 agonist)group and carotid artery endothelial injury+SR9009(n=5 in each group). They were treated with DMSO or SR9009(100 mg·kg-1·d-1)via intraperitoneal injection for 14 days after operation,respectively. The degree of carotid intimal hyperplasia was measured by HE staining 28 days after operation. Results NR1D1 overexpression significantly reduced the percentage of Ki-67-positive cells(P<0.01),total cell number(P<0.01)and slowed down the rate of wound-healing(P<0.01). NR1D1 overexpression significantly inhibited the expression of β-catenin(P<0.05). After the expression of β-catenin was restored by SKL2001,the inhibitory effects of NR1D1 overexpression on the proliferation and migration of AFs were abolished(P<0.01). Enhanced activity of NR1D1 significantly ameliorated intimal hyperplasia after carotid endothelial injury(P<0.01). Conclusion NR1D1 may inhibit the proliferation and migration of AFs via suppressing the expression of β-catenin.
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Objective:To evaluate the validity of adventitial collagen cross-linking by glutaraldehyde(GA) to reduce intimal hyperplasia of vein graft in a rabbit carotid artery bypass graft model.Methods:Harvesting 36 segments of the external jugular vein and 6 segments of the internal carotid artery with 3 cm length from the New Zealand white rabbits. The veins were randomly divided into 6 groups and underwent adventitial collagen cross-linking by 0.3% glutaraldehyde for 0 min, 1 min, 2 min, 3 min, 4 min, and 5 min, respectively. All vessel segments were subjected to biomechanical tests and pathological tests. Carotid artery bypass graft models were established in 24 New Zealand white rabbits including crosslinked group(n=12) and non-crosslinked group(n=12). The vein grafts were obtained for pathological examination 4 weeks after models feeding, and the intimal hyperplasia of vein graft was evaluated.Results:Adventitial cross-linking increased fiber density of adventitia significantly, and increased the stiffness of the veins as the time of cross-linking increased. And in the high strain region(strain ratio 1.4-1.8), the mechanical curve of veins receiving 3min cross-linking was similar to that of the carotid artery. The patent rate of the vein grafts of rabbit models was 100% after 4 weeks. Comparing with non-crosslinked group, the intimal and medial thickness of vein grafts in crosslinked group were reduced remarkably[(78.83±9.02)μm vs.(140.19±19.90)μm, (43.75±5.05)μm vs.(58.35 ± 8.61) μm, P<0.01). Conclusion:Adventitial collagen cross-linking by GA can enhance the mechanical strength of the jugular vein, and reduce the intimal hyperplasia of the jugular vein grafts in rabbit models.
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We sometimes encounter the case that we have to make an anastomosis between a prosthetic graft and an autologous vein graft in revascularization of a lower extremity. However, it is said that the intimal hyperplasia in the anastomosis site of a prosthetic graft and autologous vein graft has a tendency to become severe in the long term postoperatively. We herein report a case in which a vein cuff (St. Mary's boot) technique was very useful to prevent recurrent stenosis due to intimal hyperplasia. No recurrence of stenosis in repair lesion has been detected for 7.5 years after operation.
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Objective: To investigate the pharmacodynamics and possible targets of Astragali Radix (AR)-Angelicae Sinensis Radix (ASR) compatibility in improving intimal hyperplasia by using network pharmacology. Methods: The TCMSP database was used to obtain the active constituents of AR-ASR, and the Pharmmaper database was used to collect the targets corresponding to the active ingredients. Targets related to intimal hyperplasia were collected by Genecards, DigSeE, and OMIM databases, and compared with drug targets, common parts were screened as predictive targets for drug action. The use of STRING was to obtain the predicted relationship between target proteins, and to screen out the core targets according to the size of the relationship. Using the Cytoscape 3.6.1 software, a "drug-component-disease-target" network map and a core target interaction network map were drawn. KEGG pathway enrichment analysis and GO biological process analysis of core targets were performed using R language. Results: A total of 193 drug targets and 487 disease targets were obtained from the 20 active components of AR-ASR, mainly targeting EGFR, ESR1, ALB, MAPK8, PGR and other targets, involving PI3K-Akt, MAPK, Ras and other signaling pathways to play a role in anti-vascular intimal hyperplasia. Conclusion: Based on the network pharmacology, the possible targets and signaling pathways for the improvement of intimal hyperplasia by AR-ASR can be preliminarily explored, which may provide a reference for the study of the mechanism of the combination of AR and ASR.
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Objective • To investigate the effect of albendazole (ABZ) on mouse femoral arteries restenosis and explore its possible mechanism. Methods • Vascular smooth muscle cells (VSMCs) were cultured in vitro with 0.5 and 1 μmol/L ABZ, and evaluated for cell proliferation, migration, and apoptosis by MTT, Transwell assay, and Annexin V-PI staining flow cytometry, respectively; and Western blotting was also used for the analysis of phosphorylation mechanism of cytoskeleton proteins cofilin (CFL) and myosin light chain (MLC). Stenosis was established in the unilateral femoral artery of 10-week-old wildtype male C57BL/6 mice by perivascular cuff placement and high fat chow breeding for 4 weeks. After successful modeling, mice were randomly divided into control group (equal volume of solvent) and ABZ group (1.5 mg/d) for gavage, and femoral arteries were collected 4 weeks later for H-E histological analysis of intimal area, medial area, and intima/media (I/M) ratio to clarify the severity of restenosis. Results • Both 0.5 and 1 μmol/L ABZ could significantly inhibit the proliferation and migration of VSMCs (both P<0.05), while 0.5 μmol/L had no significant effect on the apoptosis of VSMCs. ABZ gavage could significantly reduce the neointimal area and I/M ratio in the restenosis mice, while there were no effects on the median area. Both 0.5 and 1 μmol/L ABZ treatment could significantly inhibit CFL dephosphorylation and MLC phosphorylation, which showed a concentration-dependent trend (both P<0.05). Conclusion • ABZ inhibits VSMCs migration and intimal hyperplasia, via affecting the phosphorylation of cytoskeleton protein CFL and MLC, thereby resulting in therapeutic effects on restenosis of mice.
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<p><b>OBJECTIVE</b>To investigate the effect and potential mechanisms of rutaecarpine (Rut) in a rat artery balloon-injury model.</p><p><b>METHODS</b>The intimal hyperplasia model was established by rubbing the endothelia with a balloon catheter in the common carotid artery (CCA) of rats. Fifty rats were randomly divided into five groups, ie. sham, model, Rut (25, 50 and 75 mg/kg) with 10 rats of each group. The rats were treated with or without Rut (25, 50, 75 mg/kg) by intragastric administration for 14 consecutive days following injury. The morphological changes of the intima were evaluated by hematoxylin-eosin staining. The expressions of proliferating cell nuclear antigen (PCNA) and smooth muscle (SM) α-actin in the ateries were assayed by immunohistochemical staining. The mRNA expressions of c-myc, extracellular signal-regulated kinase 2 (ERK2), MAPK phosphatase-1 (MKP-1) and endothelial nitric oxide synthase (eNOS) were determined by real-time reverse transcription-polymerase chain reaction. The protein expressions of MKP-1 and phosphorylated ERK2 (p-ERK2) were examined by Western blotting. The plasma contents of nitric oxide (NO) and cyclic guanosine 3',5'-monophosphate (cGMP) were also determined.</p><p><b>RESULTS</b>Compared with the model group, Rut treatment significantly decreased intimal thickening and ameliorated endothelial injury (P<0.05 or P<0.01). The positive expression rate of PCNA was decreased, while the expression rate of SM α-actin obviously increased in the vascular wall after Rut (50 and 75 mg/kg) administration (P<0.05 or P<0.01). Furthermore, the mRNA expressions of c-myc, ERK2 and PCNA were downregulated while the expressions of eNOS and MKP-1 were upregulated (P<0.05 or P<0.01). The protein expressions of MKP-1 and the phosphorylation of ERK2 were upregulated and downregulated after Rut (50 and 75 mg/kg) administration (P<0.05 or P<0.01), respectively. In addition, Rut dramatically reversed balloon injury-induced decrease of NO and cGMP in the plasma (P<0.05 or P<0.01).</p><p><b>CONCLUSION</b>Rut could inhibit the balloon injury-induced carotid intimal hyperplasia in rats, possibly mediated by promotion of NO production and inhibiting ERK2 signal transduction pathways.</p>
Subject(s)
Animals , Male , Actins , Metabolism , Carotid Arteries , Metabolism , Pathology , Carotid Artery Injuries , Drug Therapy , Genetics , Pathology , Cyclic GMP , Blood , Disease Models, Animal , Gene Expression Regulation , Hyperplasia , Indole Alkaloids , Pharmacology , Therapeutic Uses , Nitric Oxide , Blood , Phosphorylation , Proliferating Cell Nuclear Antigen , Metabolism , Quinazolines , Pharmacology , Therapeutic Uses , RNA, Messenger , Genetics , Metabolism , Rats, Sprague-Dawley , Tunica Intima , PathologyABSTRACT
Objective • To establish New Zealand rabbit autogenous vein graft model and observe the changes of intimal hyperplasia in vein grafts at different time after grafting. Methods • 35 female New Zealand rabbits of 10 weeks old were randomly divided into 5 groups (7 rats in each group), i.e. postoperative 7 d group, postoperative 14 d group, postoperative 28 d group, postoperative 60 d group and normal control group. An animal model of external jugular vein common carotid artery bypass grafting was established, and the model construction steps were elaborated and optimized. Hematoxylin-eosin (H-E) staining was used to observe the intimal thickness after surgery and immunofluorescence staining was used to observe the expression of α-smooth muscle actin (α-SMA), which was one of the vascular smooth muscle cell (VSMC) differentiation marker protein. The effect of model construction was finally evaluated. Results • In addition to the normal control group, the other 28 New Zealand rabbits were successfully completed the vein graft operation. All the grafted veins kept unblocked except for one graft in postoperative 7 d group developed thrombosis, and the success rate was 96.4% (27/28). H-E staining and immunofluorescence staining showed significant intimal hyperplasia after vein grafting. Compared with the normal control group, the intimal thickness of the vein grafts was significantly increased (all P=0.000) and the fluorescence intensity of α-SMA was significantly enhanced at each time group after surgery. Conclusion • New Zealand rabbit vein graft intimal hyperplasia modeling has an ideal success rate and good repeatability, which provides an ideal experimental model for studying the mechanism and prevention of restenosis after vein grafting.
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OBJECTIVES: To analyze the histological changes observed in venous grafts subjected to arterial blood flow as a function of the duration of the postoperative period to optimize their use in free flap reconstructions. METHOD: Twenty-five rats (7 females and 18 males) underwent surgery. Surgeries were performed on one animal per week. Five weeks after the first surgery, the same five animals were subjected to an additional surgery to assess the presence or absence of blood flow through the vascular loop, and samples were collected for histological analysis. This cycle was performed five times. RESULTS: Of the rats euthanized four to five weeks after the first surgery, no blood flow was observed through the graft in 80% of the cases. In the group euthanized three weeks after the first surgery, no blood flow was observed in 20% of the cases. In the groups euthanized one to two weeks after the first surgery, blood flow through the vascular loop was observed in all animals. Moreover, intimal proliferation tended to increase with the duration of the postoperative period. Two weeks after surgery, intimal proliferation increased slightly, whereas strong intimal proliferation was observed in all rats evaluated five weeks after surgery. CONCLUSION: Intimal proliferation was the most significant change noted in venous grafts as a function of the duration of the postoperative period and was directly correlated with graft occlusion. In cases in which vascular loops are required during free flap reconstruction, both procedures should preferably be performed during the same surgery.
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Animals , Male , Female , Carotid Arteries/physiopathology , Carotid Arteries/surgery , Jugular Veins/physiopathology , Jugular Veins/transplantation , No-Reflow Phenomenon/diagnosis , Regional Blood Flow/physiology , Vascular Grafting/methods , Anastomosis, Surgical , Carotid Arteries/pathology , Fibrosis , Jugular Veins/pathology , Microsurgery/methods , Neovascularization, Physiologic , Postoperative Period , Rats, Wistar , Reproducibility of Results , Time Factors , Treatment Outcome , Vascular Grafting/adverse effectsABSTRACT
The aims of the present study were to determine the effects of heparin-derived oligosaccharides (HDOs) on vascular intimal hyperplasia (IH) in balloon-injured carotid artery and to elucidate the underlying mechanisms of action. An animal model was established by rubbing the endothelia within the common carotid artery (CCA) in male rabbits. The rabbits were fed a high-cholesterol diet. Arterial IH was determined by histopathological changes to the CCA. Serum lipids were detected using an automated biochemical analysis. Expressions of mRNAs for vascular endothelial growth factor (VEGF), basic fibroblast growth factor (bFGF), vascular cell adhesion molecule-1 (VCAM-1), monocyte chemoattractant protein-1 (MCP-1), scavenger receptor class B type I (SR-BI), and ATP-binding cassette transporter A1 (ABCA-1) were analyzed using reverse transcription polymerase chain reaction assays. Expressions of VEGF, VCAM-1, MCP-1, SR-BI and ABCA-1 proteins were analyzed by Western blotting. Enzyme-linked immunosorbent assays were used to quantify expression levels of VEGF and bFGF. Our results showed that administration of HDO significantly inhibited CCA histopathology and restenosis induced by balloon injury. The treatment with HDOs significantly decreased the mRNA and protein expression levels of VEGF, bFGF, VCAM-1, MCP-1, and SR-BI in the arterial wall; however, ABCA-1 expression level was elevated. HDO treatment led to a reduction in serum lipids (total cholesterol, triglycerides, high-density and low-density lipoproteins). Our results from the rabbit model indicated that HDOs could ameliorate IH and underlying mechanism might involve VEGF, bFGF, VCAM-1, MCP-1, SR-BI, and ABCA-1.
Subject(s)
Animals , Male , Rabbits , ATP Binding Cassette Transporter 1 , Carotid Artery Injuries , Drug Therapy , Pathology , Chemokine CCL2 , Heparin , Therapeutic Uses , Hyperplasia , Oligosaccharides , Therapeutic Uses , Tunica Intima , Pathology , Vascular Cell Adhesion Molecule-1 , Vascular Endothelial Growth Factor AABSTRACT
[Objective]To study the effects of Caspase-1 specific inhibitor AC-YVAD-CMK on intimal hyperplasia after carotid artery balloon injury in rats and its possible mechanism.[Methods]A total of 33 male adult SD rats were randomly divided into sham group,balloon injury group and balloon injury+AC-YVAD-CMK group. Using the method of balloon injury to establish rat carotid ar?tery intimal hyperplasia animal model,rats were sacrificed and blood vessels were harvested 14 days after operation. Fifteen vascular segments embedded in OCT and the intima to media(I/M)area ratio of neointima was measured by hematoxylin-eosin(HE)staining;18 vascular segments were harvested and the expression of NLRP3 inflammasome,cleaved-Caspase-1,interleukin(IL)-1βand IL-18 were measured by Western blot.[Results]HE staining showed that AC-YVAD-CMK significantly inhibited the degree of intimal hyperplasia compared with the balloon injury group[(0.78 ± 0.13)vs(1.52 ± 0.14);P=0.000]. The expression of NLRP3 inflamma?some was increased in balloon injury group while the AC-YVAD-CMK attenuates the expression of NLRP3(P=0.009);The expres?sion of cleaved-Caspase-1 was in line with the expression of NLRP3(P=0.000). The levels of pro-inflammatory cytokines IL-1βand IL-18 in balloon injury+AC-YVAD-CMK group were significantly lower than those in the balloon injury group(P=0.000).[Conclusion]AC-YVAD-CMK can attenuate intimal hyperplasia after balloon injury of carotid artery in rats,which might be related to its effect on inhibiting the activation of Caspase-1,which could affect the release of pro-inflammatory cytokine of IL-1βand IL-18.
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Objective To investigate the inhibitory effect of a new antihypertensive drug on carotid artery intimal hyperplasia in balloon-injured rats and its possible mechanism.Methods A total of 48 SD rats were randomly divided as follows:sham operation group,model group,low-dose Azilsartan medoxomil group and high-dose Azilsartan medoxomil group(n =12).The rats in sham operateion group and model group were treated by by gavage with 3ml normal saline every day,and rats in low-dose Azilsartan medoxomil group and high-dose Azilsartan medoxomil group were treated by by gavage at adose of 2mg/kg and 4mg/kg Azilsartan medoxomil(3ml) every day.14 and 28 days after operation,we can observe the morphological changes of the injured arteries by HE staining and measure intimal area (IA),medial area(MA),the intimal/medial area ratio (IA/MA).The expression of PCNA,TLR4,NF-κB p65 in each group were detected by immunohistochemistry and the plasma level of TNF-α,IL-6 were detected by enzyme-linked immunosorbent assay (ELISA).Results Compared with the model group,the intimal area and the intimal / medial area ratio were significantly reduced in the low-dose group and hige-dose group (P ＜ 0.05).The expression of PCNA,TLR4 and NF-κB p65 in carotid artery were significantly lower (P ＜ 0.05).The plasma level of TNF-α、IL-6 were significantly lower (P ＜ 0.05).Compared with the sham operation group,the intimal area and the intimal/medial area ratio were significantly increased in the operation group (P ＜ 0.05) and the expression of PCNA,TLR4 and NF-κB p65 in carotid artery were significantly increased (P ＜0.05).The plasma level of TNF-α、IL-6 were significantly increased (P ＜ 0.05).Conclusion Azilsartan medoxomil can alleviate the incidence of vascular restenosis.The mechanism of action possibly was related to reducing the expression of inflammatory factors such as TNF-α,IL-6 by TLR4/NF-κB pathway and inhibiting the carotid artery intimal hyperplasia.
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Objective: To study the expression pattern of apolipoprotein J (Apo J) in rat's model of vascular restenosis after cartid balloon dilation. Methods: A total of 40 Wistar rats were randomly divided into 2 groups: Experimental group, the rat's model of carotid artery injury was established by 2 F Fogarty balloon catheter scratching in right carotid artery and Control group, the rats received sham operation without catheter scratching. n=20 in each group. Right carotid artery tissue was taken at 1, 2, 3, 4 weeks after the operation respectively and 5 rats were used for each time point. The morphological changes were measured by HE staining, protein and gene expressions of Apo J were examined by immunohistochemistry and qRT-PCR. Results: Compared with Control group, at each time point Experimental group had obvious intimal hyperplasia and up-regulated protein and gene expressions of Apo J, P<0.05. In Experimental group, with prolonged time of injury, consistent endometrial hyperplasia was observed and it reached the maximum at 4 weeks after operation; the peak protein and gene expressions of Apo J was found at 3 weeks after operation, then decreased at certain point at 4 weeks after operation, P<0.05. Conclusion: Apo J might be closely related to intimal hyperplasia after vascular injury, high expression of vascular Apo J was mainly derived from vascular smooth muscle cell synthesis, it could be a kind of compensation with protective role and might be used as a new biological target for treating vascular retenosis after percutaneous coronary intervention.
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Objective · To observe the vascular structure before autogenous arteriovenous fistula (AVF) construction in patients with end-stage renal disease (ESRD) and analyze the risk factors of the pre-existing venous neointimal hyperplasia. Methods · The 8 vein samples were screened from 20 ESRD patients at their first time of the AVF construction (non-stenosis group), and the other 8 vein samples were screened from 15 ESRD patients at their at least second time of the AVF repair operation (stenosis group). Sections were prepared and stained with hematoxylin & eosin (H-E) or Masson's trichrome for observation. The intimal thickness was measured by the cellSens software, and its correlation with patients' renal function, calcium-phosphorus metabolism, iron metabolism and inflammatory reaction in the non-stenosis group were analyzed. Results · In the non-stenosis group, there were varying degrees of intimal hyperplasia in 5 (62.5%) cases, loss of endothelial cell layer in 3 (37.5%) cases, and vascular wall replacement by collagenous with atrophy or loss of muscle layer in 5 (62.5%) cases. In the stenosis group, almost all vein samples showed general thickening of the wall and 2 (25.0%) totally lost the muscle layer. Avg It of those two groups were statistically significant (P<0.01). In the non-stenosis group, both of average I/M thickness and average I/M area were negatively related to glomerular filtration rate (GFR) (P<0.05) and positively related to serum phosphorus and calcium-phosphorus product (P<0.05). Conclusion · Some apparently normal vein of ESRD patients showed varying degrees of intimal hyperplasia before AVF construction. The intimal hyperplasia had a remarkable correlation with GFR or calcium-phosphorus metabolism. Early intervention of the intimal hyperplasia prior to AVF construction may be a new prevention and control means.
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Objective: To investigate the inhibitory effects of ginsenoside Re on intimal hyperplasia in balloon-injuried rats and further explore the role of TGF-β1/Smads signaling pathway in this protection. Methods: Fifty SD rats were randomly divided into five groups, including Sham operation group, model group, ginsenoside Re low, medium, and high-dose groups. The injured model of carotid artery intima was established by 2F balloon catheters in each group except the sham operation group. One day after model was established, animals were daily ig administered with distilled water in model group, Sham operation group, and ginsenoside Re (12.5 mg/kg, 25 mg/kg and 50 mg/kg) groups. Two weeks later, animals were sacrificed and the injured artery was taken for HE staining. The histopathological changes were observed and the lumen area, intima area, and media area as well as the ratio of intimal area/media area were detected. The expression of transforming growth factors β1 (TGF-β1), SMAD family member 2 (Smad 2) and Smad family member 3 (Smad 3) were measured by real time RT-PCR and immunohistochemistry. Results: Compared with the Sham operation group, the vessel cavity in the model group was narrower (P < 0.01); Compared with the model group, the medium and high dose of ginsenoside Re obviously alleviated vascular intimal hyperplasia (P < 0.05). Compared with the Sham operation group, the mRNA and protein expressions levels of TGF-β1, Smad 2, and Smad 3 in model group were higher (P < 0.01), which were obviously decreased in the medium and high-dose ginsenoside Re (P < 0.05). Conclusion: Ginsenoside Re could alleviate the vascular neointimal hyperplasia through suppressing the TGF-β1/Smads signaling pathway.
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Objective To observe the effects of different compatibility ratios of Astragali Radix and Angelicae Sinensis Radix on vascular intimal hyperplasia; To ascertain the effective compatibility of Astragali Radix and Angelicae Sinensis Radix for antagonizing vascular intimal hyperplasia. Methods SD rats were divided into different groups by baseline geometric design method: Astragali Radix and Angelicae Sinensis Radix different compatibility ratios groups, Astragali Radix group, Angelicae Sinensis Radixgroup, positive medicinegroup and sham-operation group. A model of intimal hyperplasia of thoracoabdominal aorta was established by balloon catheter injury in vascular endothelium of rats. Then the thoracoabdominal aorta was taken out after gavage of Astragali Radix and Angelicae Sinensis Radix with different compatibility ratios for 14 days. Bloodletting was used to take thoracoabdominal aorta. Masson staining and Morphometric methods were used to analyze the intimal hyperplasia. Results IA, IT, HRIA and HRIT increased 14 day after intimal injury. Compared with the model group, IA, IT, HRIA and HRIT in Angelicae Sinensis Radix group, Astragali Radix and Angelicae Sinensis Radix 1:2 group, Astragali Radix and Angelicae Sinensis Radix 1:5 group, Astragali Radix and Angelicae Sinensis Radix 1:1 group and Astragali Radix and Angelicae Sinensis Radix 5:1 group were lower, and the effects of Astragali Radix and Angelicae Sinensis Radix 1:1 ratio were strongest. The effects on intimal hyperplasia in Astragali Radix group and Astragali Radix and Angelicae Sinensis 2:1 group had no significant differences compared with model group. Conclusion Astragali Radix and Angelicae Sinensis can inhibit vascular intimal hyperplasia in a certain compatibility ratios, and the effects of Astragali Radix and Angelicae Sinensis Radix 1:1 on intimal hyperplasia are the best.
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Objective To observe the degradation time and the intimal hyperplasia of biodegradable magnesium alloy stent (MPM) implanted in the abdominal aorta of experimental rabbits.Methods A total of 24 New Zealand white rabbits were randomly divided into four groups (30 d,60 d,90 d and 180 d) with 6 rabbits in each group.In cach rabbit one MPM stent was implanted in the abdominal aorta at the level of one cm below the left renal artery.Reexamination of abdominal aortography with DSA was separately performed at 30,60,90 and 180 d after stent implantation to check the stent condition.The rabbits of each group were sacrificed at the corresponding scheduled day,the stenting segment of aorta of each rabbit was removed and the specimen was sent for microscopic examination.The experimental results were analyzed with SPSS20.0 software.Results All the 24 experimental rabbits survived.During the follow-up period the stent showed gradual degradation changes,and basically complete degradation was not observed until to 180 days.Meanwhile,the intimal hyperplasia reached its peak at 90 days after implantation.The abdominal aorta remained unobstructed during the whole process of degradation.Conclusion The time of complete degradation for MPM stent is 182 days,which is long enough to meet the needs of vascular positive remodeling.
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The radiocephalic arteriovenous fistula (AVF) provides optimal vascular access for hemodialysis; it has a higher long-term patency rate and fewer complications than other vascular access methods. However, the AVF has a high primary failure rate. The presence of small-diameter vessels at anastomosis sites is an important risk factor for AVF failure. However, in a recent study, despite selecting an adequate artery and vein for creating an AVF by routine preoperative vascular mapping, AVF maturation and primary failure occurred. Thus, pre-existing arteriosclerosis at AVF anastomosis sites likely contributes to AVF failure. In this review, we discuss the relationship between pathologic changes and AVF patency in hemodialysis patients. Because arteriosclerosis of the major arteries such as the coronary and carotid arteries is associated with cardiovascular mortality, we also review the impact of arteriosclerosis of upper arm arteries at AVF anastomosis sites on cardiovascular mortality in hemodialysis patients.
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Humans , Arm , Arteries , Arteriosclerosis , Arteriovenous Fistula , Carotid Arteries , Mortality , Renal Dialysis , Risk Factors , Vascular Calcification , VeinsABSTRACT
[ ABSTRACT] AIM:To investigate the inhibitory effect of ginsenoside Re on intimal hyperplasia induced by bal-loon-injury and to explore the role of NF-κB p65 signaling pathway in the process.METHODS:SD rats (n=40) were di-vided into 5 groups randomly: sham operation group, model group, low-dose ginsenoside Re group, middle-dose ginsen-oside Re group and high-dose ginsenoside Re group.The carotid artery intima injury model was established by 2F balloon catheters in all groups except the sham operation group.The day after modeling, the animals in model group and sham op-eration group were administered intragastrically with distilled water, and the rats in low-dose, middle-dose and high-dose ginsenoside Re groups were given ginsenoside Re at doses of 12.5 mg/kg, 25mg/kg and 50 mg/kg, respectively.After 14 continuous days, the morphological changes of the injured arteries were observed by HE staining and the lumen area, intima area and media area as well as the ratio of intimal area/media area were determined.The expression of tumor necrosis fac-tor-α( TNF-α) and interleukin-1β( IL-1β) were detected by real-time PCR.The proliferating cell nuclear antigen ( PC-NA) and nuclear factor-kappa B ( NF-κB) p65 were examined by immunohistochemistry.RESULTS:Compared with sham operation group, the vessel cavity was narrowed (P sion of PCNA and NF-κB p65 were decreased in medium and high-dose ginsenoside Re groups (P<0.05).CONCLU-SION:Ginsenoside Re inhibits the vascular neointimal hyperplasia induced by balloon-injury in rats, and the molecular mechanism may be related to the inhibition of NF-κB p65 signaling pathway.
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Objective: To investigate the effects of asragaloside IV (AS-IV) on cultured vascular smooth muscle cells (VSMCs) and neointima hyperplasia in the carotid artery of rats after ballon injury and explore the inhibitory mechanisms. Methods: For next related researches, primary cultures of VSMCs were prepared from the thoracoabdominal aorta of rats using explant method. Taking the recombinant rat tumor necrosis factor (TNF-α, 100 ng/mL ) as the stimulating factor, the model of VSMCs proliferation was established by TNF-α inducer in vitro and the effects of AS-IV (0, 0.5, 5, 25, and 50 μg/mL) on the VSMCs proliferation induced by TNF-α were determined by CCK-8 method. Rat carotid artery balloon injury model was prepared by Fogarty (2F) balloon catheter. Fifty healthy male Sprague-Dawley rats were randomly divided into five groups: a Sham-operation group (Sham), a model group (model), and three AS-IV-treated (20, 40, and 60 mg/kg) groups. Three days before the surgery, 1% CMC, AS-IV 20, 40, and 60 mg/kg were ig administered to each group once daily for continuous 17 d. Fifteen days after the surgery, rats were killed, and the carotid arterys were harvested. Hematoxylin-elsin staining was carried out to observe the pathomorphological change in vascular intima. The measurement of lumen area, intimal area, intimal area/medium film area were measured by computer image analysis system; Immunohistochemistry staining was performed to measure the expression of proliferating cell nuclear antigen (PCNA) and platelet-derived growth factor-BB (PDGF-BB). Results: The proliferative activity of VSMCs was obviously increased in the TNF-α group under the stimulation of TNF-α. There was a significant difference compared with the control group (P < 0.01). However, when pretreated with AS-IV ahead of time, we found that AS-IV significantly inhibited TNF-α-induced VSMCs proliferation in a dose- and time-dependent manner compared to the TNF-α group. Compared with the model group, the area of intima, the ratio of intima to media (I/M), and the expression of PCNA and PDGF-BB decreased significantly (P < 0.05) in AS-IV groups. Conclusion: AS-IV exerts the inhibitory effects on VSMCs proliferation in a dose- and time-dependent manner. AS-IV significantly inhibits the neointimal hyperplasia in rat carotid artery. It might be partially attributed to the inhibition of proliferation. It may be one of the mechanisms of inhibiting the proliferation of carotid intima in rats induced by balloon injury that AS-IV inhibits the expression of growth factor PDGF-BB.
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Objective To establish a close clinical and easy to operate animal artery bypass grafting model by using vascular anastomosis wheel.Methods 15 rabbits that weighted 2.5-3.5 kg were studied.Each animal underwent an end-toend anastomosis of jugular vein and carotid artery by vascular anastomosis wheel.Carotid ultrasound and flow detection were taken immediately and 2 months after surgery respectively,as well as morphology and pathology were recorded to analyze and evaluate the intimal hyperplasia of vein graft and arteriovenous anastomotic site.Results 14 rabbits were successfully established CABG model,however 1 rabbit died of respiratory inhibition caused of excessive anesthesia.Compared with normal carotid artery,the vein bridge showed significantly lower blood flow [(50.81 ± 1.33) ml/min vs.(70.59 ± 0.68) ml/min,P ＜0.01,higher PI(2.15 ±0.07vs.1.22 ±0.04,P ＜0.01)] immediately after surgery.Compared with the vein grafts immediately after surgery,the vein grafts 2 months after surgery showed significantly lower blood flow [(27.46 ± 2.15) ml/min vs.(50.81 ± 1.33) ml/min,P ＜ 0.01].Compared with normal jugular vein,the vein grafts 2 months after surgery showed significantly higher intimal hyperplasia[(160.30 ± 1.78) μm vs.(49.06 ± 2.76) μm,P ＜ 0.01],and higher number of elastic plates(12.36 ± 0.25vs.3.21 ± 0.15,P ＜ 0.01).Conclusion The use of vascular anastomosis wheel to establish an artery bypass graft model can imitate the pathological changes of vein grafts after CABG,which can provide an ideal animal model for various researches on vein grafts.