Intimal hyperplasia(IH)is a negative vascular remodeling after arterial injury.IH occasionally occurs in elastase-induced abdominal aortic aneurysm(AAA)mouse models.This study aims to clarify the incidence and histolo...Intimal hyperplasia(IH)is a negative vascular remodeling after arterial injury.IH occasionally occurs in elastase-induced abdominal aortic aneurysm(AAA)mouse models.This study aims to clarify the incidence and histological characteristics of IH in aneurysmal mice.A retrospective study was conducted by including 42 male elastaseinduced mouse AAA models.The IH incidence,aortic diameters with or without IH,and hyperplasia lesional features of mice were analyzed.Among 42 elastase-induced AAA mouse models,10 mice developed mild IH(24%)and severe IH was found in only 2 mice(5%).The outer diameters of the AAA segments in mice with and without IH did not show significant difference.Both mild and severe IH lesions show strong smooth muscle cell positive staining,but endothelial cells were occasionally observed in severe IH lesions.There was obvious macrophage infiltration in the IH lesions of the AAA mouse models,especially in mice with severe IH.However,only a lower numbers of T cells and B cells were found in the IH lesion.Local cell-secreted matrix metalloproteinases(MMP)2 was highly expressed in all IH lesions,but MMP9 was only overexpressed in severe lesions.In conclusion,this study is the first to demonstrate the occurrence of aneurysmal IH and its histological characteristics in an elastaseinduced mouse AAA model.This will help researchers better understand this model,and optimize it for use in AAA-related research.展开更多
BACKGROUND Primary intimal sarcoma of the pulmonary artery is a rare malignant tumor originating from the pulmonary artery,which has a low incidence rate and is easily misdiagnosed as pulmonary embolism.There is no st...BACKGROUND Primary intimal sarcoma of the pulmonary artery is a rare malignant tumor originating from the pulmonary artery,which has a low incidence rate and is easily misdiagnosed as pulmonary embolism.There is no standard protocol for the treatment of primary intimal sarcoma of the pulmonary artery.CASE SUMMARY This study reports a patient with primary intimal sarcoma of the pulmonary artery who was admitted to our hospital in 2017.The clinical characteristics,diagnosis,treatment and outcome of the patient were retrospectively analyzed.The patient was a Chinese Han male aged 44 years.He had three consecutive episodes of syncope,and was thus admitted to a local hospital.Computed tomography pulmonary angiography showed multiple lesions with abnormal densities in the pulmonary trunk,left pulmonary artery,mediastinum and pericardium,which were consistent with recurrence after tumor resection.He underwent surgery,and was pathologically diagnosed with intimal sarcoma of the pulmonary artery.He relapsed 3 mo after surgery,and apatinib was administered.His condition was stable after 4 mo,with tolerable and controllable adverse reactions.He subsequently died 19 mo after surgery.CONCLUSION Primary intimal sarcoma of the pulmonary artery has no specific clinical or imaging manifestations.The diagnosis of this disease depends on histopathology and immunohistochemistry,and has a poor clinical prognosis.Surgical treatment is currently a favorable option for primary intimal sarcoma of the pulmonary artery,and targeted therapy may provide new insights for the development of effective treatment methods.展开更多
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...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 mR NAs for vascular endothelial growth factor(VEGF), basic fibroblast growth factor(bF GF), 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 b FGF. Our results showed that administration of HDO significantly inhibited CCA histopathology and restenosis induced by balloon injury. The treatment with HDOs significantly decreased the m RNA and protein expression levels of VEGF, b FGF, 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, b FGF, VCAM-1, MCP-1, SR-BI, and ABCA-1.展开更多
Pulmonary artery intimal sarcoma(PAIS) is a rare tumor with a very poor prognosis. Clinical and radiological findings usually mimic thromboembolic disease, leading to diagnostic delays. The treatment of choice is surg...Pulmonary artery intimal sarcoma(PAIS) is a rare tumor with a very poor prognosis. Clinical and radiological findings usually mimic thromboembolic disease, leading to diagnostic delays. The treatment of choice is surgery, and adjuvant chemotherapy and radiotherapy have limited results. We report the case of a 48-year-old male patient, initially suspected with pulmonary thromboembolism. The angio-CT revealed a filling defect in the pulmonary artery trunk. The patient underwent surgery, resulting in with complete resection of the mass with a diagnosis of PAIS. The tumor progressed rapidly in the lung, requiring surgery of multiple lung metastases. The patient was treated with stereotactic body radiation therapy(SBRT) on two occasions for new pulmonary lesions. In the last follow-up(4 years after initial diagnosis), the patient was disease-free. In conclusion, SBRT proved to be an alternative treatment to metastasectomy, allowing palliative chemotherapy to be delayed or omitted, which may result in improved quality of life.展开更多
Objective To investigate the effect of no-touch harvesting technique in reducing vein graft intimal hyperplasia. Methods This longitudinal trial compared graft angiostenosis of two groups undergoing jugular vein to ca...Objective To investigate the effect of no-touch harvesting technique in reducing vein graft intimal hyperplasia. Methods This longitudinal trial compared graft angiostenosis of two groups undergoing jugular vein to carotid artery interposition grafting in rabbit model. Conventional group:12 rabbits had their veins stripped,distended,and stored in heparinized saline solution. No-touch group:12 rabbits had veins removed with surrounding tissues,but were not distended,and stored in heparinized blood. The grafts were removed 4 weeks following grafting,and morphometry and immunohistochemistry assessment were performed. Results The intimal thickness,degree of angiostenosis and proliferation index of vascular smooth muscle cells of no-touch group were significantly reduced (P<0.01) compared with those of the conventional group. The proliferating cell nuclear antigen positive-staining cells were significantly increased (P<0.01) in the conventional group compared with whose in the no-touch group. Conclusion Harvesting the vein graft with no-touch harvesting technique could significantly reduce intimal hyperplasia of the vein graft.展开更多
Objective: To explore the alleviation of arterial intimal hyperplasia and improvement of outflow by inserting an autogenous vein cuff between poly tetraflu oroethylene (PTFE) graft and arteri al an astomosis. Methods:...Objective: To explore the alleviation of arterial intimal hyperplasia and improvement of outflow by inserting an autogenous vein cuff between poly tetraflu oroethylene (PTFE) graft and arteri al an astomosis. Methods: Twenty-four hindlimbs of 12 mongrel dogs were randomly divided into control group and experimental group. Sole PTFE bypasses were made in the control group, an autologous vein cuff was inserted in the distal anastomosis in the experimental group. Eight weeks after operation, angiography was made and specimens were harvested, histomorphological studies under microscope and picture analysis with computer were carried out, scanning electromicroscopy on the vein cuff was made. Results: Angiography demonstrated the patency of control and experimental group was 16. 7% and 66. 7%, respectively; Computer gave the intimal thickness: (483. 5 ± 67. 3) μm and (147. 4 ± 38. 6) μm, respectively; no obvious change was seen in medial thickness; area of intimal hyperplasia was (5217 ± 1 123) (pixel) and (31 17 ± 890) (pixel), respectively, accounting (80. 9 ± 17. 2)% and (47. 7 ± 13. 7)% of the sectional area of vessel lumen. The interpositional vein was arteriolization. Conclusion: The interpositional autologous vein cuff can obviously mitigate the arterial intimal hyperplasia after PTFE bypasses, improving postoperative patency of vascular surgery.展开更多
Objective: To design an extravascular trestle model coated phosphorus-32, an isotope radiating beta rays, and investigate its effects on intimal hyperplasia of autologous vein grafts. Methods: ETA cDNA was used as a g...Objective: To design an extravascular trestle model coated phosphorus-32, an isotope radiating beta rays, and investigate its effects on intimal hyperplasia of autologous vein grafts. Methods: ETA cDNA was used as a gene probe specific to vascular SMCs on the basis of in situ hybridization. The femoral veins were transplanted reversely into colateral femoral arteries in rabbits, and the animals were divided into control, chemical agents and phosphorus-32 groups. The morphometry was applied to calculate the ETA cDNA expression and intimal thickness. Spearman correlation method was utilized to investigate their relationship. Results: Intimal thickness in grafts of phosphorus-32 group was markedly reduced. Additionally, intimal ETA gene expression was also decreased in beta rays group. The values increased at a slower rate significantly different from that of control and aspirin groups (P<0.01). The correlation of ETA cDNA expression and intimal thickness exhibited a strongly positive relation. Conclusion: Beta rays in extravascular model could remarkably inhibit intimal thickening and SMC proliferation. The correlation is an indirect evidence indicating that intimal hyperplasia composed of SMCs proliferation. It suggests that ETA cDNA expression could be a quantitative estimation of vascular SMC because of its specifics.展开更多
A 66-year-old female with a 1-month history of increasing fatigue, dyspnea on exertion, and palpitations presented with clinical signs of heart failure. Chest computed tomography (CT) revealed a large, mobile left atr...A 66-year-old female with a 1-month history of increasing fatigue, dyspnea on exertion, and palpitations presented with clinical signs of heart failure. Chest computed tomography (CT) revealed a large, mobile left atrial (LA) mass attached to the mitral valve causing severe mitral stenosis and mitral regurgitation. The mass was surgically debulked and the mitral valve was replaced. Pathology revealed a poorly differentiated malignant spindle cell neoplasm with diffuse nuclear positivity of MDM2 and multifocal positivity of CDK4, consistent with intimal sarcoma. This case seeks to describe an uncommon presentation of a rare malignancy, and the surgical and medical management of the disease.展开更多
Objective Pentamethylquercetin (PMQ) has a role in cardiovascular protection.We investigate the effects of 3,3 ’,4 ’,5,7 pentamethylquercetin,a derivative of PMQ,on intimal hyperplasia of the vein grafts in rats bot...Objective Pentamethylquercetin (PMQ) has a role in cardiovascular protection.We investigate the effects of 3,3 ’,4 ’,5,7 pentamethylquercetin,a derivative of PMQ,on intimal hyperplasia of the vein grafts in rats both in vivo and in vitro. Methods The proliferation of vascular smooth muscle cells (VSMC) was induced with Ang Ⅱ (0.1 μmol/L,24 h) while PMQ was administrated at six different dosages (0.1,0.3,1,3,10 and 30 μmoL/L).展开更多
Open vascular reconstructions(OVR),including bypass grafts and dialysis access,are standard treatments for cardiovascular and renal diseases.Unfortunately,OVR often fail largely due to intimal hyperplasia(IH),and ther...Open vascular reconstructions(OVR),including bypass grafts and dialysis access,are standard treatments for cardiovascular and renal diseases.Unfortunately,OVR often fail largely due to intimal hyperplasia(IH),and there are no clinical methods to prevent this complication.Perivascular drug administration during OVR presents a promising strategy for IH suppression.However,durations of drug release from carriers are generally short whereas sustained efficacy is essential for clinical success.This raises a critical question in clinical translation:can IH suppression be realistically maintained long-term(e.g.,over 6 months)with short-term perivascular interventions?To address this question,we modified a rat vein-graft model to prolong IH progression.We then applied Pericelle,a nanoparticle/hydrogel hybrid system that we developed for perivascular delivery of rapa-mycin,an established IH-inhibitory drug.Surprisingly,despite short(~3-month)drug release,Pericelle demonstrated IH suppression throughout 3,6,and 9 months with IH reduced from 115.58±27.89 to 40.34±5.18 at 9 months(P<0.05,n=6 rats),as indicated by morphometric analysis.Live animal ultrasonography showed the same trend.Consistently,histone-3 lysine-27 trimethylation,an epigenetic mark associated with IH progression,was decreased at 6 months after Pericelle treatment.Moreover,Pericelle exhibited promising ef-ficacy in mitigating IH in a porcine model of arteriovenous fistula that mimics dialysis access.These results suggest that Pericelle-mediated suppression of IH in rat vein-grafts extends much beyond drug release,offering potential solutions to longstanding translational challenges in reducing OVR failure.展开更多
Transradial access (TRA) has emerged as the preferred vascular access route forcoronary angiography and percutaneous coronary interventions due to itssuperior safety profile compared to transfemoral access. However, i...Transradial access (TRA) has emerged as the preferred vascular access route forcoronary angiography and percutaneous coronary interventions due to itssuperior safety profile compared to transfemoral access. However, its widespreadadoption raises concerns regarding structural alterations in the radial artery,which may impact long-term vascular health and future procedural feasibility.TRA is associated with histopathologic changes in the arterial wall, such asintimal injury and hyperplasia, medial remodeling and adventitial inflammation,collectively contributing to radial artery remodeling. Moreover, TRA can inducechanges in radial artery lumen diameter driven by an inflammatory response dueto arterial puncture and mechanical friction during the procedure. Nonetheless, amore clinically significant consequence is radial artery occlusion, which is influencedby various procedural and patient-related factors. Strategies to minimizeremodeling include meticulous pre-procedural ultrasound assessment to ensureappropriate sheath-to-artery size matching, periprocedural pharmacologicalinterventions and implementation of patent hemostasis techniques. This reviewsynthesizes current knowledge regarding the mechanisms, clinical implications,and preventive strategies related to radial artery remodeling following TRA. Further research is needed toelucidate the long-term consequences of radial artery remodeling and to refine preventive strategies for preservingradial artery patency and its suitability for future interventions.展开更多
Pulmonary tumour thrombotic microangiopathy(PTTM)is a rare but under-recognised cause of rapidly progressive pulmonary hypertension(PH)and cor pulmonale,characterised by diffuse obstruction of small pulmonary arteries...Pulmonary tumour thrombotic microangiopathy(PTTM)is a rare but under-recognised cause of rapidly progressive pulmonary hypertension(PH)and cor pulmonale,characterised by diffuse obstruction of small pulmonary arteries by metastatic tumour cells.These tumour emboli lead to obstructive intimal proliferation and in situ thrombosis within the pulmonary vasculature,further compromising the overall permeability of the pulmonary vascular bed and exacerbating PH.[1]The clinical and imaging manifestations of PTTM often overlap with those of other causes of PH,including chronic thromboembolic PH,pulmonary veno-occlusive disease and pulmonary capillary haemangiomatosis,often leading to diagnostic delays.展开更多
The long arm of human chromosome 12 contains a region that has been found to be amplified in a number of different tumors, including osteosarcomas and soft tissue sarcomas. There are more than 5 genes located in this ...The long arm of human chromosome 12 contains a region that has been found to be amplified in a number of different tumors, including osteosarcomas and soft tissue sarcomas. There are more than 5 genes located in this area such as CDK2, CDK4, WNT1, MDM2 and WNTIOb. CDK4 gene consists of eight exons, of which the start codon is located in the beginning of exon 2 and the stop codon in the a member of the Ser-Thr catalytic domain extends beginning of exon 8. CDK4 is protein kinase family and its from amino acid 6 to 295.展开更多
Objective： To investigate the effect and potential mechanisms of rutaecarpine （Rut） in a rat artery balloon-injury model. Methods： The intimal hyperplasia model was established by rubbing the endothelia with a bal...Objective： To investigate the effect and potential mechanisms of rutaecarpine （Rut） in a rat artery balloon-injury model. Methods： 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） oL-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 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. Results： 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 downragulated 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）. Conclusion： 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.展开更多
Implantable vascular devices are widely used in clinical treatments for various vascular diseases. However, current approved clinical implantable vascular devices generally have high failure rates primarily due to the...Implantable vascular devices are widely used in clinical treatments for various vascular diseases. However, current approved clinical implantable vascular devices generally have high failure rates primarily due to their surface lacking inherent functional endothelium. Here, inspired by the pathological mechanisms of vascular device failure and physiological functions of native endothelium, we developed a new generation of bioactive parylene (poly(p-xylylene))-based conformal coating to address these challenges of the vascular devices. This coating used a polyethylene glycol (PEG) linker to introduce an endothelial progenitor cell (EPC) specific binding ligand LXW7 (cGRGDdvc) onto the vascular devices for preventing platelet adhesion and selectively capturing endogenous EPCs. Also, we confirmed the long-term stability and function of this coating in human serum. Using two vascular disease-related large animal models, a porcine carotid artery interposition model and a porcine carotid artery-jugular vein arteriovenous graft model, we demonstrated that this coating enabled rapid generation of self-renewable “living” endothelium on the blood contacting surface of the expanded polytetrafluoroethylene (ePTFE) grafts after implantation. We expect this easy-to-apply conformal coating will present a promising avenue to engineer surface properties of “off-the-shelf” implantable vascular devices for long-lasting performance in the clinical settings.展开更多
Small-diameter tissue-engineered vascular grafts(sdTEVGs)with hyperglycemia resistance have not been constructed.The intimal hyperplasia caused by hyperglycemia remains problem to hinder the patency of sdTEVGs.Here,in...Small-diameter tissue-engineered vascular grafts(sdTEVGs)with hyperglycemia resistance have not been constructed.The intimal hyperplasia caused by hyperglycemia remains problem to hinder the patency of sdTEVGs.Here,inspired by bionic regulation of nerve on vascular,we found the released neural exosomes could inhibit the abnormal phenotype transformation of vascular smooth muscle cells(VSMCs).The transformation was a prime culprit causing the intimal hyperplasia of sdTEVGs.To address this concern,sdTEVGs were modified with an on-demand programmable dual-responsive system of ultrathin hydrogels.An external primary Reactive Oxygen Species(ROS)-responsive Netrin-1 system was initially triggered by local inflammation to induce nerve remolding of the sdTEVGs overcoming the difficulty of nerve regeneration under hyperglycemia.Then,the internal secondary ATP-responsive DENND1A(guanine nucleotide exchange factor)system was turned on by the neurotransmitter ATP from the immigrated nerve fibers to stimulate effective release of neural exosomes.The results showed nerve fibers grow into the sdTEVGs in diabetic rats 30 days after transplantation.At day 90,the abnormal VSMCs phenotype was not detected in the sdTEVGs,which maintained long-time patency without intima hyperplasia.Our study provides new insights to construct vascular grafts resisting hyperglycemia damage.展开更多
Pulmonary artery intimal sarcoma （PALS） is a very rare but lethal disease, firstly described by Mandelstarnmin 1923.1 Since then, less than 300 cases have been reported worldwide. Due to similar clinical presentatio...Pulmonary artery intimal sarcoma （PALS） is a very rare but lethal disease, firstly described by Mandelstarnmin 1923.1 Since then, less than 300 cases have been reported worldwide. Due to similar clinical presentations, it is very difficult to distinguish with pulmonary thromboembolism （PTE）, leading to inappropriate treatments such as anticoagulation and thrombolysis.2-5Although with improvement of imaging modalities, the diagnosis of PAIS is still based on pathological examination, and the majority of specimens are taken by surgery or autopsy.展开更多
Objective: The intimal hyperplasia caused by migration and proliferation of the smooth muscle cells play a most important role in the stenosis of the vein grafts. This study is to explore how the C myc oncogene and it...Objective: The intimal hyperplasia caused by migration and proliferation of the smooth muscle cells play a most important role in the stenosis of the vein grafts. This study is to explore how the C myc oncogene and its protein contribute to the intimal hyperplasia after the jugular vein is transplanted to the abdominal aorta and to assess the effect of Mithramycin on the intimal hyperplasia. Methods: In 60 Wistar rats, a 0.8 cm segment of the right jugular vein graft was interposed at the level of the abdominal aorta. The experiment group received Mithramycin (150 μg/kg IP) 1 h before and after the operation. The control group received normal saline, specimens of vein graft at 2 and 6 h postoperatively were subjected respectively to in situ hybridization. The vein grafts 4 weeks after operation were perfusion fixed. The specimens were stained with hemotoxylin eosin and the computer morphologic analysis system was used to evaluate the degree of intimal thickening. Immunohistochemistry studies of muscle specific α actin, C myc protein and 5 Bromodeoxyuridine were performed. Results: The areas of neointimal and the ratios of neointimal to medial area were significantly smaller and lower in the Mithramycin treated than in the control rats (P< 0.05 ). The 5 Brdu labeling rate between the two groups were also different significantly (P< 0.05 ). Muscle specific α actin showed that the smooth muscle cells formed the most area of myointimal hyperplasia. Steady state C myc mRNA level was increased from 2 h to 6 h postoperatively. The positive rate of the placebo treated group was higher significantly than that of the Mithramycin treated group (P< 0.05 ). Conclusions: Mithramycin may effectively inhibits transcription of C myc in proliferating vascular smooth muscle cells and could be useful in the prevention of restenosis after vascularization. These results support the hypothesis that systemic administration of Mithramycin might immediately prevent intimal proliferation.展开更多
This study explores the impact mechanism and practical strategies of biophilic design in dining spaces on customer emotional experiences.Based on environmental psychology theory,it analyzes how natural elements improv...This study explores the impact mechanism and practical strategies of biophilic design in dining spaces on customer emotional experiences.Based on environmental psychology theory,it analyzes how natural elements improve emotional states through mechanisms such as reducing stress hormones and enhancing brainwave activity,confirming that multisensory collaborative design can increase customer satisfaction to 83.6%.Combining typical case studies with cross-cultural research,specific implementation plans for dynamic landscapes,material combinations,and light environment optimization are proposed,providing a theoretical basis and technical references for dining space design.展开更多
基金supported by Shaanxi Provincial Natural Science Foundation(2023-CX-PT-17 to Sihai Zhao)Natural Science Foundation of Xi'an Jiaotong University Foundation(YXJLRH2022073 to Sihai Zhao)Project of Key Laboratory of Medical Large Animal Models of Guangdong Province(Klmlam 202204 to Sihai Zhao)。
文摘Intimal hyperplasia(IH)is a negative vascular remodeling after arterial injury.IH occasionally occurs in elastase-induced abdominal aortic aneurysm(AAA)mouse models.This study aims to clarify the incidence and histological characteristics of IH in aneurysmal mice.A retrospective study was conducted by including 42 male elastaseinduced mouse AAA models.The IH incidence,aortic diameters with or without IH,and hyperplasia lesional features of mice were analyzed.Among 42 elastase-induced AAA mouse models,10 mice developed mild IH(24%)and severe IH was found in only 2 mice(5%).The outer diameters of the AAA segments in mice with and without IH did not show significant difference.Both mild and severe IH lesions show strong smooth muscle cell positive staining,but endothelial cells were occasionally observed in severe IH lesions.There was obvious macrophage infiltration in the IH lesions of the AAA mouse models,especially in mice with severe IH.However,only a lower numbers of T cells and B cells were found in the IH lesion.Local cell-secreted matrix metalloproteinases(MMP)2 was highly expressed in all IH lesions,but MMP9 was only overexpressed in severe lesions.In conclusion,this study is the first to demonstrate the occurrence of aneurysmal IH and its histological characteristics in an elastaseinduced mouse AAA model.This will help researchers better understand this model,and optimize it for use in AAA-related research.
文摘BACKGROUND Primary intimal sarcoma of the pulmonary artery is a rare malignant tumor originating from the pulmonary artery,which has a low incidence rate and is easily misdiagnosed as pulmonary embolism.There is no standard protocol for the treatment of primary intimal sarcoma of the pulmonary artery.CASE SUMMARY This study reports a patient with primary intimal sarcoma of the pulmonary artery who was admitted to our hospital in 2017.The clinical characteristics,diagnosis,treatment and outcome of the patient were retrospectively analyzed.The patient was a Chinese Han male aged 44 years.He had three consecutive episodes of syncope,and was thus admitted to a local hospital.Computed tomography pulmonary angiography showed multiple lesions with abnormal densities in the pulmonary trunk,left pulmonary artery,mediastinum and pericardium,which were consistent with recurrence after tumor resection.He underwent surgery,and was pathologically diagnosed with intimal sarcoma of the pulmonary artery.He relapsed 3 mo after surgery,and apatinib was administered.His condition was stable after 4 mo,with tolerable and controllable adverse reactions.He subsequently died 19 mo after surgery.CONCLUSION Primary intimal sarcoma of the pulmonary artery has no specific clinical or imaging manifestations.The diagnosis of this disease depends on histopathology and immunohistochemistry,and has a poor clinical prognosis.Surgical treatment is currently a favorable option for primary intimal sarcoma of the pulmonary artery,and targeted therapy may provide new insights for the development of effective treatment methods.
基金supported by the National Basic Research Funds(Nos.JKYJ2013044 and JKZ2011013)the Significant New Drugs Innovation Support Program of the National Science and Technology Project of China(No.2012ZX09502001-004)the Priority Academic Program Development of Jiangsu Higher Education Institution
文摘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 mR NAs for vascular endothelial growth factor(VEGF), basic fibroblast growth factor(bF GF), 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 b FGF. Our results showed that administration of HDO significantly inhibited CCA histopathology and restenosis induced by balloon injury. The treatment with HDOs significantly decreased the m RNA and protein expression levels of VEGF, b FGF, 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, b FGF, VCAM-1, MCP-1, SR-BI, and ABCA-1.
文摘Pulmonary artery intimal sarcoma(PAIS) is a rare tumor with a very poor prognosis. Clinical and radiological findings usually mimic thromboembolic disease, leading to diagnostic delays. The treatment of choice is surgery, and adjuvant chemotherapy and radiotherapy have limited results. We report the case of a 48-year-old male patient, initially suspected with pulmonary thromboembolism. The angio-CT revealed a filling defect in the pulmonary artery trunk. The patient underwent surgery, resulting in with complete resection of the mass with a diagnosis of PAIS. The tumor progressed rapidly in the lung, requiring surgery of multiple lung metastases. The patient was treated with stereotactic body radiation therapy(SBRT) on two occasions for new pulmonary lesions. In the last follow-up(4 years after initial diagnosis), the patient was disease-free. In conclusion, SBRT proved to be an alternative treatment to metastasectomy, allowing palliative chemotherapy to be delayed or omitted, which may result in improved quality of life.
文摘Objective To investigate the effect of no-touch harvesting technique in reducing vein graft intimal hyperplasia. Methods This longitudinal trial compared graft angiostenosis of two groups undergoing jugular vein to carotid artery interposition grafting in rabbit model. Conventional group:12 rabbits had their veins stripped,distended,and stored in heparinized saline solution. No-touch group:12 rabbits had veins removed with surrounding tissues,but were not distended,and stored in heparinized blood. The grafts were removed 4 weeks following grafting,and morphometry and immunohistochemistry assessment were performed. Results The intimal thickness,degree of angiostenosis and proliferation index of vascular smooth muscle cells of no-touch group were significantly reduced (P<0.01) compared with those of the conventional group. The proliferating cell nuclear antigen positive-staining cells were significantly increased (P<0.01) in the conventional group compared with whose in the no-touch group. Conclusion Harvesting the vein graft with no-touch harvesting technique could significantly reduce intimal hyperplasia of the vein graft.
文摘Objective: To explore the alleviation of arterial intimal hyperplasia and improvement of outflow by inserting an autogenous vein cuff between poly tetraflu oroethylene (PTFE) graft and arteri al an astomosis. Methods: Twenty-four hindlimbs of 12 mongrel dogs were randomly divided into control group and experimental group. Sole PTFE bypasses were made in the control group, an autologous vein cuff was inserted in the distal anastomosis in the experimental group. Eight weeks after operation, angiography was made and specimens were harvested, histomorphological studies under microscope and picture analysis with computer were carried out, scanning electromicroscopy on the vein cuff was made. Results: Angiography demonstrated the patency of control and experimental group was 16. 7% and 66. 7%, respectively; Computer gave the intimal thickness: (483. 5 ± 67. 3) μm and (147. 4 ± 38. 6) μm, respectively; no obvious change was seen in medial thickness; area of intimal hyperplasia was (5217 ± 1 123) (pixel) and (31 17 ± 890) (pixel), respectively, accounting (80. 9 ± 17. 2)% and (47. 7 ± 13. 7)% of the sectional area of vessel lumen. The interpositional vein was arteriolization. Conclusion: The interpositional autologous vein cuff can obviously mitigate the arterial intimal hyperplasia after PTFE bypasses, improving postoperative patency of vascular surgery.
文摘Objective: To design an extravascular trestle model coated phosphorus-32, an isotope radiating beta rays, and investigate its effects on intimal hyperplasia of autologous vein grafts. Methods: ETA cDNA was used as a gene probe specific to vascular SMCs on the basis of in situ hybridization. The femoral veins were transplanted reversely into colateral femoral arteries in rabbits, and the animals were divided into control, chemical agents and phosphorus-32 groups. The morphometry was applied to calculate the ETA cDNA expression and intimal thickness. Spearman correlation method was utilized to investigate their relationship. Results: Intimal thickness in grafts of phosphorus-32 group was markedly reduced. Additionally, intimal ETA gene expression was also decreased in beta rays group. The values increased at a slower rate significantly different from that of control and aspirin groups (P<0.01). The correlation of ETA cDNA expression and intimal thickness exhibited a strongly positive relation. Conclusion: Beta rays in extravascular model could remarkably inhibit intimal thickening and SMC proliferation. The correlation is an indirect evidence indicating that intimal hyperplasia composed of SMCs proliferation. It suggests that ETA cDNA expression could be a quantitative estimation of vascular SMC because of its specifics.
文摘A 66-year-old female with a 1-month history of increasing fatigue, dyspnea on exertion, and palpitations presented with clinical signs of heart failure. Chest computed tomography (CT) revealed a large, mobile left atrial (LA) mass attached to the mitral valve causing severe mitral stenosis and mitral regurgitation. The mass was surgically debulked and the mitral valve was replaced. Pathology revealed a poorly differentiated malignant spindle cell neoplasm with diffuse nuclear positivity of MDM2 and multifocal positivity of CDK4, consistent with intimal sarcoma. This case seeks to describe an uncommon presentation of a rare malignancy, and the surgical and medical management of the disease.
文摘Objective Pentamethylquercetin (PMQ) has a role in cardiovascular protection.We investigate the effects of 3,3 ’,4 ’,5,7 pentamethylquercetin,a derivative of PMQ,on intimal hyperplasia of the vein grafts in rats both in vivo and in vitro. Methods The proliferation of vascular smooth muscle cells (VSMC) was induced with Ang Ⅱ (0.1 μmol/L,24 h) while PMQ was administrated at six different dosages (0.1,0.3,1,3,10 and 30 μmoL/L).
基金supported by the NIH Center for Accelerated Innovations-Cleveland Clinic(NCAI-CC)award 1UH54HL119810-06(1118-SUB)to K.C.K.and L.-W.G.The Ohio State University Accelerator award(ECG20170069)to K.C.K.and L.-W.G.+2 种基金the Ohio Development Services Agency fund(GRT00051721)to L.-W.GThis research also partially involved funding support from NIH awards R01HL129785(to K.C.K.,S.G.,and L.-W.G.)R01HL168405(to L.-W.G.,K.C.K.,and S.G.).
文摘Open vascular reconstructions(OVR),including bypass grafts and dialysis access,are standard treatments for cardiovascular and renal diseases.Unfortunately,OVR often fail largely due to intimal hyperplasia(IH),and there are no clinical methods to prevent this complication.Perivascular drug administration during OVR presents a promising strategy for IH suppression.However,durations of drug release from carriers are generally short whereas sustained efficacy is essential for clinical success.This raises a critical question in clinical translation:can IH suppression be realistically maintained long-term(e.g.,over 6 months)with short-term perivascular interventions?To address this question,we modified a rat vein-graft model to prolong IH progression.We then applied Pericelle,a nanoparticle/hydrogel hybrid system that we developed for perivascular delivery of rapa-mycin,an established IH-inhibitory drug.Surprisingly,despite short(~3-month)drug release,Pericelle demonstrated IH suppression throughout 3,6,and 9 months with IH reduced from 115.58±27.89 to 40.34±5.18 at 9 months(P<0.05,n=6 rats),as indicated by morphometric analysis.Live animal ultrasonography showed the same trend.Consistently,histone-3 lysine-27 trimethylation,an epigenetic mark associated with IH progression,was decreased at 6 months after Pericelle treatment.Moreover,Pericelle exhibited promising ef-ficacy in mitigating IH in a porcine model of arteriovenous fistula that mimics dialysis access.These results suggest that Pericelle-mediated suppression of IH in rat vein-grafts extends much beyond drug release,offering potential solutions to longstanding translational challenges in reducing OVR failure.
文摘Transradial access (TRA) has emerged as the preferred vascular access route forcoronary angiography and percutaneous coronary interventions due to itssuperior safety profile compared to transfemoral access. However, its widespreadadoption raises concerns regarding structural alterations in the radial artery,which may impact long-term vascular health and future procedural feasibility.TRA is associated with histopathologic changes in the arterial wall, such asintimal injury and hyperplasia, medial remodeling and adventitial inflammation,collectively contributing to radial artery remodeling. Moreover, TRA can inducechanges in radial artery lumen diameter driven by an inflammatory response dueto arterial puncture and mechanical friction during the procedure. Nonetheless, amore clinically significant consequence is radial artery occlusion, which is influencedby various procedural and patient-related factors. Strategies to minimizeremodeling include meticulous pre-procedural ultrasound assessment to ensureappropriate sheath-to-artery size matching, periprocedural pharmacologicalinterventions and implementation of patent hemostasis techniques. This reviewsynthesizes current knowledge regarding the mechanisms, clinical implications,and preventive strategies related to radial artery remodeling following TRA. Further research is needed toelucidate the long-term consequences of radial artery remodeling and to refine preventive strategies for preservingradial artery patency and its suitability for future interventions.
文摘Pulmonary tumour thrombotic microangiopathy(PTTM)is a rare but under-recognised cause of rapidly progressive pulmonary hypertension(PH)and cor pulmonale,characterised by diffuse obstruction of small pulmonary arteries by metastatic tumour cells.These tumour emboli lead to obstructive intimal proliferation and in situ thrombosis within the pulmonary vasculature,further compromising the overall permeability of the pulmonary vascular bed and exacerbating PH.[1]The clinical and imaging manifestations of PTTM often overlap with those of other causes of PH,including chronic thromboembolic PH,pulmonary veno-occlusive disease and pulmonary capillary haemangiomatosis,often leading to diagnostic delays.
文摘The long arm of human chromosome 12 contains a region that has been found to be amplified in a number of different tumors, including osteosarcomas and soft tissue sarcomas. There are more than 5 genes located in this area such as CDK2, CDK4, WNT1, MDM2 and WNTIOb. CDK4 gene consists of eight exons, of which the start codon is located in the beginning of exon 2 and the stop codon in the a member of the Ser-Thr catalytic domain extends beginning of exon 8. CDK4 is protein kinase family and its from amino acid 6 to 295.
基金Supported by National Natural Science Foundation of China(No.81160528)Administration of Traditional Chinese Medicine of Guizhou Province foundation,China(No.2009-79)
文摘Objective： To investigate the effect and potential mechanisms of rutaecarpine （Rut） in a rat artery balloon-injury model. Methods： 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） oL-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 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. Results： 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 downragulated 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）. Conclusion： 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.
基金supported by the UC Davis School of Medicine Dean’s Fellowship award,the Science Translation and Innovative Research(STAIR)grant offered by UC Davis Venture Catalyst,the National Heart,Lung,And Blood Institute under Award Number T32 HL086350 and U54HL 119893 through UC BRAID Center for Accelerated Innovation Technology Grant,and California Institute for Regenerative Medicine(CIRM)grant(TRAN3-13332).The authors would also like to thank the Combinatorial Chemistry Shared Resource at University of California Davis for assistance with design and synthesis of peptides and their derivativesUtilization of this Shared Resource was supported by the UC Davis Comprehensive Cancer Center Support Grant awarded by the National Cancer Institute(P30CA093373).
文摘Implantable vascular devices are widely used in clinical treatments for various vascular diseases. However, current approved clinical implantable vascular devices generally have high failure rates primarily due to their surface lacking inherent functional endothelium. Here, inspired by the pathological mechanisms of vascular device failure and physiological functions of native endothelium, we developed a new generation of bioactive parylene (poly(p-xylylene))-based conformal coating to address these challenges of the vascular devices. This coating used a polyethylene glycol (PEG) linker to introduce an endothelial progenitor cell (EPC) specific binding ligand LXW7 (cGRGDdvc) onto the vascular devices for preventing platelet adhesion and selectively capturing endogenous EPCs. Also, we confirmed the long-term stability and function of this coating in human serum. Using two vascular disease-related large animal models, a porcine carotid artery interposition model and a porcine carotid artery-jugular vein arteriovenous graft model, we demonstrated that this coating enabled rapid generation of self-renewable “living” endothelium on the blood contacting surface of the expanded polytetrafluoroethylene (ePTFE) grafts after implantation. We expect this easy-to-apply conformal coating will present a promising avenue to engineer surface properties of “off-the-shelf” implantable vascular devices for long-lasting performance in the clinical settings.
基金We would like to thank Xing Shen and Yaqing Tang in the Innovative Drug Research Center of Chongqing University and Jing Zhou in the Department of Physiology,Basic Medical College,Peking University,for their support with the work.Thank Zhang San from Shiyanjia Lab(www.shiyanjia.com)for the modulus analysis.This work was supported by the National Key Research and Development Plan Young Scientists Program(No:2017YFA0106000)The National Science Fund for Outstanding Young Scholars(No.31822021)+1 种基金the National Science Foundation of China(No:31771057)and The National Key Research and Development Plan(No:2016YFC1101100).
文摘Small-diameter tissue-engineered vascular grafts(sdTEVGs)with hyperglycemia resistance have not been constructed.The intimal hyperplasia caused by hyperglycemia remains problem to hinder the patency of sdTEVGs.Here,inspired by bionic regulation of nerve on vascular,we found the released neural exosomes could inhibit the abnormal phenotype transformation of vascular smooth muscle cells(VSMCs).The transformation was a prime culprit causing the intimal hyperplasia of sdTEVGs.To address this concern,sdTEVGs were modified with an on-demand programmable dual-responsive system of ultrathin hydrogels.An external primary Reactive Oxygen Species(ROS)-responsive Netrin-1 system was initially triggered by local inflammation to induce nerve remolding of the sdTEVGs overcoming the difficulty of nerve regeneration under hyperglycemia.Then,the internal secondary ATP-responsive DENND1A(guanine nucleotide exchange factor)system was turned on by the neurotransmitter ATP from the immigrated nerve fibers to stimulate effective release of neural exosomes.The results showed nerve fibers grow into the sdTEVGs in diabetic rats 30 days after transplantation.At day 90,the abnormal VSMCs phenotype was not detected in the sdTEVGs,which maintained long-time patency without intima hyperplasia.Our study provides new insights to construct vascular grafts resisting hyperglycemia damage.
文摘Pulmonary artery intimal sarcoma （PALS） is a very rare but lethal disease, firstly described by Mandelstarnmin 1923.1 Since then, less than 300 cases have been reported worldwide. Due to similar clinical presentations, it is very difficult to distinguish with pulmonary thromboembolism （PTE）, leading to inappropriate treatments such as anticoagulation and thrombolysis.2-5Although with improvement of imaging modalities, the diagnosis of PAIS is still based on pathological examination, and the majority of specimens are taken by surgery or autopsy.
文摘Objective: The intimal hyperplasia caused by migration and proliferation of the smooth muscle cells play a most important role in the stenosis of the vein grafts. This study is to explore how the C myc oncogene and its protein contribute to the intimal hyperplasia after the jugular vein is transplanted to the abdominal aorta and to assess the effect of Mithramycin on the intimal hyperplasia. Methods: In 60 Wistar rats, a 0.8 cm segment of the right jugular vein graft was interposed at the level of the abdominal aorta. The experiment group received Mithramycin (150 μg/kg IP) 1 h before and after the operation. The control group received normal saline, specimens of vein graft at 2 and 6 h postoperatively were subjected respectively to in situ hybridization. The vein grafts 4 weeks after operation were perfusion fixed. The specimens were stained with hemotoxylin eosin and the computer morphologic analysis system was used to evaluate the degree of intimal thickening. Immunohistochemistry studies of muscle specific α actin, C myc protein and 5 Bromodeoxyuridine were performed. Results: The areas of neointimal and the ratios of neointimal to medial area were significantly smaller and lower in the Mithramycin treated than in the control rats (P< 0.05 ). The 5 Brdu labeling rate between the two groups were also different significantly (P< 0.05 ). Muscle specific α actin showed that the smooth muscle cells formed the most area of myointimal hyperplasia. Steady state C myc mRNA level was increased from 2 h to 6 h postoperatively. The positive rate of the placebo treated group was higher significantly than that of the Mithramycin treated group (P< 0.05 ). Conclusions: Mithramycin may effectively inhibits transcription of C myc in proliferating vascular smooth muscle cells and could be useful in the prevention of restenosis after vascularization. These results support the hypothesis that systemic administration of Mithramycin might immediately prevent intimal proliferation.
文摘This study explores the impact mechanism and practical strategies of biophilic design in dining spaces on customer emotional experiences.Based on environmental psychology theory,it analyzes how natural elements improve emotional states through mechanisms such as reducing stress hormones and enhancing brainwave activity,confirming that multisensory collaborative design can increase customer satisfaction to 83.6%.Combining typical case studies with cross-cultural research,specific implementation plans for dynamic landscapes,material combinations,and light environment optimization are proposed,providing a theoretical basis and technical references for dining space design.
