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The incidence rate and histological characteristics of intimal hyperplasia in elastase-induced experimental abdominal aortic aneurysms in mice

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Animal Models and Experimental Medicine 2024年第3期7卷 388-395页

作者： Meng Li Panpan Wei Kexin Li Haole Liu Naqash Alam Haiwen Hou Jie Deng Baohui Xu Enqi Liu Sihai Zhao Yankui Li Laboratory Animal Center Xi'an Jiaotong UniversityXi'anChina Department of Vascular Surgery The Second Hospital of Tianjin Medical UniversityTianjinChina Department of Cardiology The Second Affiliated Hospital of Xi'an Jiaotong UniversityXi'anChina Department of Vascular Surgery Stanford University School of MedicineStanfordCaliforniaUSA

intimal hyperplasia(IH)is a negative vascular remodeling after arterial *** occasionally occurs in elastase-induced abdominal aortic aneurysm(AAA)mouse *** 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 *** IH incidence,aortic diameters with or without IH,and hyperplasia lesional features of mice were *** 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 *** mild and severe IH lesions show strong smooth muscle cell positive staining,but endothelial cells were occasionally observed in severe IH *** was obvious macrophage infiltration in the IH lesions of the AAA mouse models,especially in mice with severe ***,only a lower numbers of T cells and B cells were found in the IH *** cell-secreted matrix metalloproteinases(MMP)2 was highly expressed in all IH lesions,but MMP9 was only overexpressed in severe *** conclusion,this study is the first to demonstrate the occurrence of aneurysmal IH and its histological characteristics in an elastaseinduced mouse AAA *** will help researchers better understand this model,and optimize it for use in AAA-related research.

关键词： abdominal aortic aneurysms animal model histology intimal hyperplasia

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A bio-instructive parylene-based conformal coating suppresses thrombosis and intimal hyperplasia of implantable vascular devices

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Bioactive Materials 2023年第10期28卷 467-479页

作者： Dake Hao Jonathan Lin Ruiwu Liu Christopher Pivetti Kaeli Yamashiro Linda M.Schutzman Junichiro Sageshima Mimmie Kwong Nataliya Bahatyrevich Diana L.Farmer Misty D.Humphries Kit S.Lam Alyssa Panitch Aijun Wang Department of Surgery School of MedicineUniversity of California DavisSacramentoCA95817United States Institute for Pediatric Regenerative Medicine Shriners Hospitals for ChildrenSacramentoCA95817United States Department of Biochemistry and Molecular Medicine School of MedicineUniversity of California DavisSacramentoCA95817United States Wallace H.Coulter Department of Biomedical Engineering Georgia Institute of Technology and Emory UniversityAtlant1GA30332United States Department of Biomedical Engineering University of California DavisDavisCA95616United States

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.

关键词： Parylene coating Integrin ligand Thrombosis intimal hyperplasia Implantable vascular devices

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Programmable dual responsive system reconstructing nerve interaction with small-diameter tissue-engineered vascular grafts and inhibiting intimal hyperplasia in diabetes

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Bioactive Materials 2022年第1期7卷 466-477页

作者： Yanzhao Li Yeqin Wang Fangchao Xue Xuli Feng Zhaojing Ba Junjie Chen Zhenhua Zhou Yanhong Wang Ge Guan Guanyuan Yang Ziwei Xi Hao Tian Yong Liu Ju Tan Gang Li Xiewan Chen Mingcan Yang Wen Chen Chuhong Zhu Wen Zeng Department of Anatomy National and Regional Engineering Laboratory of Tissue EngineeringState and Local Joint Engineering Laboratory for Vascular ImplantsKey Lab for Biomechanics and Tissue Engineering of ChongqingThird Military Medical UniversityChongqing400038China Department of Cell Biology Third Military Army Medical UniversityChongqing400038China Innovative Drug Research Centre of Chongqing University Chongqing401331China Departments of Neurology Southwest HospitalThird Military Medical UniversityChongqingChina Medical English Department Third Military Medical UniversityChongqing400038China The 8th Medical Center of Chinese PLA General Hospital Beijing100091China Department of Plastic and Aesthetic Surgery Southwest HospitalThird Military Medical UniversityChongqingChina State Key Laboratory of Trauma Burn and Combined InjuryChongqingChina

Small-diameter tissue-engineered vascular grafts(sdTEVGs)with hyperglycemia resistance have not been *** intimal hyperplasia caused by hyperglycemia remains problem to hinder the patency of ***,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 *** address this concern,sdTEVGs were modified with an on-demand programmable dual-responsive system of ultrathin *** 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 ***,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 *** results showed nerve fibers grow into the sdTEVGs in diabetic rats 30 days after *** day 90,the abnormal VSMCs phenotype was not detected in the sdTEVGs,which maintained long-time patency without intima *** study provides new insights to construct vascular grafts resisting hyperglycemia damage.

关键词： sdTEVGs On-demand programmed responsive systems Neural exosomes Nerve reconstruction intimal hyperplasia

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Rutaecarpine Inhibits intimal hyperplasia in A Balloon-Injured Rat Artery Model

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Chinese Journal of Integrative Medicine 2018年第6期24卷 429-435页

作者： XU Yang CHEN Xiu-ping ZHANG Feng HOU Hua-hua ZHANG Jing-yi LIN Shu-xian SUN An-sheng Key Laboratory of Basic Pharmacology of Guizhou and Department of Pharmacology Zunyi Medical College Molecular Oncology Laboratory Eastern Hepatobiliary Surgery HospitalSecond Military Medical University Institute of Chinese Medical Sciences University of Macao

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 c

关键词： rutaecarpine balloon-injury intimal hyperplasia extracellular signal-regulated kinase 2 nitric oxide

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Heparin-derived oligosaccharide inhibits vascular intimal hyperplasia in balloon-injured carotid artery

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Chinese Journal of Natural Medicines 2017年第6期15卷 442-450页

作者： LIU Jie-Ru WU Jie YU Xin-Chao QIAN Xuan XIONG Rui WANG Hui-Fang YU Dan-Feng LIU Fei-Fei HE Shu-Ying School of Life Science and Technology China Pharmaceutical University Nanjing 210009 China

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.

关键词： Atherosclerosis Heparin-derived oligosaccharide intimal hyperplasia Balloon injury

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Reducing intimal hyperplasia in vein grafts harvested by a no-touch harvesting technique

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Journal of Pharmaceutical Analysis 2009年第2期21卷 138-140页

作者： Hai-chen Wang,Wu-jun Xue,Miao-miao Liu Department of Cardiovascular Surgery,the First Affiliated Hospital,Medical School of Xi’an Jiaotong University,Xi’an 710006,China. Department of Cardiovascular Surgery First Affiliated Hospital Medical School of Xi'an Jiao-tong University Xi'an 710006 China

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 (Pintimal hyperplasia of the vein graft.

关键词： vein graft no-touch harvesting technique intimal hyperplasia

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Circular RNA circ ASK1 acts as a microRNA-22 sponge to attenuate intimal hyperplasia by regulating TET2

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中国药理学与毒理学杂志 2019年第10期 802-803页

作者： XIA Luo-xing ZENG Zhi QIN Jing-hong LI Kang TANG Wai-ho Institute of Pediatrics Guangzhou Women and Children's Medical Centre Guangzhou Medical University

OBJECTIVE Circular RNA expression aberration has been identified in various human diseases. In this study, we investigated whether circ ASK1 could act as competing endogenous mi R-22 to regulate intimal hyperplasia. METHODS Quantitative polymerase chain reactions(q PCR) and fluorescent in situ hybridization(FISH) were conducted to detect circular ASK1(circ ASK1)expression in smooth muscle cells, mouse femoral artery and human arterial specimens. The q PCR assays, Western blotting assays, CCK-8 assays and Ed U(5-ethynyl-2′-deoxyuridine) incorporation assays were conducted to detect the functional roles of circ ASK1 in vascular smooth muscle cell function in vitro. Elastic Van Gienson and immunofluorescent assays were conducted to detect the role of circ ASK1 in intimal hyperplasia in vivo. Bioinformatics analysis, luciferase activity assays, RNA pulldown assays, and in vitro studies were conducted to reveal the mechanism of circ ASK1 on inhibiting intimal hyperplasia. RESULTS PDGF stimulation could reduce circ ASK1 expression in human(HASMC) and mouse aortic smooth muscle cells(MASMC). Moreover, circ ASK1 expression was significantly down-regulated in wireinjured femoral arteries and diseased arterial specimens were characterized by presence of SMC-rich atherosclerotic lesions. Up-regulation of circ ASK1 promoted differentiation and inhibited proliferation of mouse aortic smooth muscle cells(MASMC) in vitro. circ ASK1 overexpression in vivo alleviated intimal hyperplasia, as shown by promoting differentiation of smooth muscle *** ASK1 acted as an endogenous mi R-22 sponge to sequester and inhibit mi R-22 activity, which led to increased Tet2 expression. Knockdown of mi R-22 mimicked the effect of circ ASK1 overexpression on MASMC phenotypes in vivo and in vitro. CONCLUSION Our results reveal an important role for a novel circ ASK1/mi R-22/Tet2 axis in regulation of intimal hyperplasia. Overexpression of circ ASK1 promoted differentiation and inhibit proliferat

关键词： circular RNA circASK1 microRNA-22 vascular smooth muscle cell TET2 intimal hyperplasia

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intimal hyperplasia thickness and blood flow in an axis-deviated arterial bypass

Intimal hyperplasia thickness and blood flow in an axis-devi...

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中国畜牧兽医学会2010年学术年会——第二届中国兽医临...

作者： Zaipin Xu~1,Wei Zhao~1,Anqiang Sun~2,Xiaoyan Deng~2,Yubo Fan~2,Qingyu Wang~1, Dingkun Wang~1,Junbo Gao~1,Peng Luo~1,Yao Peng~1,Yuhuan Lv~1,Zhe Ma~1,Ke Wang~3 (1.Department of Veterinary medicine,College of Animal Science,Guizhou University, Guiyang 550025,China 2.Key Laboratory for Biomechanics and Mechanobiology of Ministry of Education, School of Biological Science and Medical Engineering, Beihang University,Beijing 100191,China 3.The First Affiliation Hospital,Dalian Medical University,Dalian 116011,China)

Extensive work has shown that slow recirculation flow zone with low wall shear stress and high oscillatory shear index occurred in a bypassed artery is an important factor for the development of intimal hyperplasia(IH) in the distal *** substantiate our hypothesis that intentionally inducing swirling flow in a bypassed artery can suppress IH development along the floor of the host artery,we constructed an axis-deviated arterial bypass(ADAB) on canine common carotid artery in which swirling flow was created in the host artery and compared it with a conventional arterial bypass(CAB) in terms of IH development along the host artery *** flows in the two bypass models were characterized *** animal experiment showed that intimal thickness was 110.50±9.62μm in the CAB group and 60.32±3.52μm in the ADAB group, *** blood flow simulation revealed that the flow structure in the host artery of the ADAB model was in the form of swirling flow that was very different from the vortex flow in the conventional model,which characterized with flow stagnation and low wall shear stress along the host artery *** swirling flow created by the axis-deviated bypass eliminated the stagnation flow and enhanced wall shear stress,hence suppressed IH development along the host artery ***,the present study has pointed out a new way to eliminate and/or suppress the slow recirculation flow zones in bypassed arteries.

关键词： Axis-deviated arterial bypass Bypass surgery intimal hyperplasia Computational fluid dynamics Swirling flow Canine

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CORRELATION BETWEEN BLOOD FLOWPATTERNS AND intimal hyperplasia AT THE DISTAL END-TO-SIDE ANASTOMOSIS

CORRELATION BETWEEN BLOOD FLOWPATTERNS AND INTIMAL HYPERPLAS...

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中国力学学会学术大会'2005

作者： Xu Zaipin Deng Xiaoyan Liu Liujun (Key Lab for Biomechanics & Tissue Engineering of Ministry of Education, Chongqing University,chongqing 400044,China) (Department of Bioengineering, Beihang Universty,Beijing 100083,China)

To clarify the relationship between intimal hyperplasia and blood flow patterns in the host artery floor of the distal end-to-side anastomosis. MATERIALS AND METHODS: 32 dogs were used to construct 30°, 45°, 60°and S-type anastomoses at the common carotid artery site with autogenous graft from the canine external jugular vein. Two months after operation, the bypassed arteries were harvested and histologic sections of the distal

关键词： artery bypass intimal hyperplasia blood flow patterns

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Research progress of CTSL in cardiovascular system

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South China Journal of Cardiology 2022年第4期23卷 290-297页

作者：滕振闫波 Clinical Medical College Jining Medical University The Center for Molecular Genetics of Cardiovascular Diseases Affiliated Hospital of Jining Medical University Shandong Provincial Sino-US Cooperation Research Center for Translational Medicine Institute of Precision Medicine Jining Medical University

Cathepsin L(CTSL) is a member of cysteine cathepsin and has endopeptidase activity. CTSL exists widely in various tissues and cells and participates in protein degradation, extracellular matrix remodeling, autophagy and other processes. With the deepening of research, it is found that CTSL is related to the occurrence of cardiovascular diseases. This article introduces the research progress of CTSL in atherosclerosis, coronary heart disease,intimal hyperplasia, dilated cardiomyopathy, abdominal aortic aneurysm, hypertension, vascular aging, in order to provide research direction for CTSL.

关键词： Cathepsin L Atherosclerosis Dilated cardiomyopathy Abdominal aortic aneurysms Hypertension intimal hyperplasia Vascular aging

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