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Diabetes pathogenesis and management:the endothelium comes of age

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Journal of Molecular Cell Biology 2021年第7期13卷 500-512页

作者： Kaitlin M.Love Eugene J.Barrett Steven K.Malin Jane E.B.Reusch Judith G.Regensteiner Zhenqi Liu Division of Endocrinology and Metabolism Department of MedicineUniversity of Virginia Health SystemCharlottesvilleVA 22908USA Department of Kinesiology and Health Rutgers UniversityNew BrunswickNJUSA Division of Endocrinology Metabolism and NutritionRutgers UniversityNew BrunswickNJUSA New Jersey Institute for Food Nutrition and HealthRutgers UniversityNew BrunswickNJUSA Institute of Translational Medicine and Research Rutgers UniversityNew BrunswickNJUSA Center for Women’s Health Research University of Colorado School of MedicineAuroraCOUSA Department of Medicine University of ColoradoAnschutz Medical CampusAuroraCOUSA Rocky Mountain Regional Veterans Affairs Medical Center AuroraCOUSA

endothelium,acting as a barrier,protects tissues against factors that provoke insulin resistance and type 2 diabetes and itself responds to the insult of insulin resistance inducers with altered *** insulin resistance and vascular dysfunction occur early in the evolution of insulin resistance-related disease,can co-exist with and even contribute to the development of metabolic insulin resistance,and promote vascular complications in those *** impact of endothelial insulin resistance and vascular dysfunction varies depending on the blood vessel size and location,resulting in decreased arterial plasticity,increased atherosclerosis and vascular resistance,and decreased tissue *** with insulin resistance and diabetes are disproportionately impacted by cardiovascular disease,likely related to differential sex-hormone endothelium ***,reducing endothelial insulin resistance and improving endothelial function in the conduit arteries may reduce atherosclerotic complications,in the resistance arteries lead to better blood pressure control,and in the microvasculature lead to less microvascular complications and more effective tissue *** diabetes therapeutic modalities,including medications and exercise training,improve endothelial insulin action and vascular *** action may delay the onset of type 2 diabetes and/or its complications,making the vascular endothelium an attractive therapeutic target for type 2 diabetes and potentially type 1 diabetes.

关键词： diabetes insulin resistance endothelium vascular function

Biomimetic epithelium/endothelium on chips

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Engineered Regeneration 2022年第2期3卷 201-216页

作者： Lina Lin Xiaocheng Wang Mengying Niu Qiaolin Wu Huan Wang Yan Zu Weijian Wang Department of Anesthesiology The First Affiliated Hospital of Wenzhou Medical UniversityWenzhou 325035China Oujiang Laboratory Zhejiang Lab for Regenerative MedicineVision and Brain HealthWenzhouZhejiang 325001China Wenzhou Institute University of Chinese Academy of SciencesWenzhouZhejiang 325001China The Eighth Affiliated Hospital Sun Yat-Sen UniversityShenzhen 518033China

Epithelium and endothelium,occupying a significant proportion of cells in the human body,play a crucial role in maintaining organs’normal structure and *** methods have been employed to study the physiology and pathology of epithelium and ***,these conventional methods,such as animal trials and two-dimensional(2D)cell culture,fail to precisely simulate the complex biology of the human body due to the species difference and lack of the native microenvironment in human systems,which is essential for cell *** overcome these limitations,epithelium/endothelium on chips have been proposed,which can mimic the pathophysiology of native human systems in a controllable *** review introduces the recent progress in epithelium/endothelium on chips,aiming to provide a comprehensive review of the fabrication and application of this *** first depict the chips’basic components,materials,and fabrication ***,we focus on different chip types,from single cell-on-chip,single organ/tissue-on-chip,to *** that,we describe the biomedical applications such as in vitro study of the physiology and interaction of organs,construction of disease models,and drug ***,the recent challenges and future outlook of epithelium/endothelium on chips are discussed.

关键词： Microfluidics Organ-on-a-chip Epithelium endothelium Biomedical application

Transplanting embryonic stem cells onto damaged human corneal endothelium

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World Journal of Stem Cells 2017年第8期9卷 127-132页

作者： Charles Hanson Arsaell Arnarsson Thorir Hardarson Ann Lindgard Mandana Daneshvarnaeini Catarina Ellerstrom Anita Bruun Ulf Stenevi Unit of Reproductive Medicine Sahlgrenska University Hospital Neuroscience Laboratory University of Akureyri Fertility Centre Scandinavia Carlanderska Hospital Department of Ophthalmology Gothenburg University Takara Bio Europe AB Arvid Wallgrens Backe 2041346 GothenburgSweden Department of Ophthalmology Lund University Hospital

AIM To investigate whether human embryonic stem cells(hESCs) could be made to attach, grow and differentiate on a human Descemet's membrane(DM).METHODS Spontaneously differentiated hESCs were transferred onto a human corneal button with the endothelial layer removed using ocular sticks. The cells were cultured on a DM for up to 15 d. The genetically engineered hESC line expressed green fluorescent protein, which facilitated identification during the culture experiments, tissue preparation, and analysis. To detect any differentiation into human corneal endothelial-like cells, we analysed the transplanted cells by immunohistochemistry using specific *** We found transplanted cells form a single layer of cells with a hexagonal shape in the periphery of the DM. The majority of the cells were negative for octamer-binding transcription factor 4 but positive for paired box 6 protein, sodium potassium adenosine triphosphatase(NaKATPase), and Zona Occludens protein 1. In four of the 18 trials, the transplanted cells were found to express CK3, which indicates that the stem cells differentiated into corneal epithelial cells in these cases. CONCLUSION It is possible to get cells originating from hESCs to become established on a human DM, where they grow and differentiate into corneal endothelial-like cells in vitro.

关键词： Embryonic stem cells Cornea Descemet’s membrane endothelium Immunohistochemistry

Spatial control of robust transgene expression in mouse artery endothelium under ultrasound guidance

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Signal Transduction and Targeted Therapy 2022年第8期7卷 2704-2706页

作者： Renfa Liu Shuai Qu Yunxue Xu Hanjoong Jo Zhifei Dai Department of Biomedical Engineering College of Future TechnologyNational Biomedical Imaging CenterPeking UniversityBeijingChina Wallace H.Coulter Department of Biomedical Engineering Georgia Institute of Technology and Emory UniversityAtlantaUSA

Dear Editor,Dysfunctional vascular endothelial cells(ECs)contribute to the pathophysiology of several cardiovascular diseases,such as atherosclerosis and its life-threatening complications.1 Gene therapy can be a valuable approach to modulate endothelial cell function for the prevention of ***,there is still a lack of method for transgene expression in vascular endothelium.2 Herein,an effective and specific strategy was established for noninvasive spatial control of transgene expression into the target region of the mouse artery without systemic spillover using an ultrasound and microbubble(MB)guided adenoassociated viral vector(UMGAAV)(Supplementary Fig.S1).To the best of our knowledge,this is the first report on noninvasive spatial control of transgene expression in arterial endothelium in vivo.

关键词： endothelium prevention atherosclerosis

Hypoxia,vascular smooth muscles and endothelium

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Acta Pharmaceutica Sinica B 2013年第1期3卷 1-7页

作者： Calvin K.Chan Paul M.Vanhoutte Department of Pharmacology and Pharmacy University of Hong KongHong KongChina Department of BIN Fusion Technology Chonbuk National UniversityJeonjuSouth Korea

Hypoxia,or the lack of oxygen,has multiple impacts on the vascular *** major molecular sensors for hypoxia at the cellular level are hypoxia inducible factor and heme *** also acts on the vasculature directly conveying its damaging effects through disruption of the control of vascular tone,particularly in the coronary circulation,enhancement of inflammatory responses and activation of coagulation *** effects could be particularly detrimental under pathological conditions such as obstructive sleep apnea and other breathing disorders.

关键词： Coronary circulation Contractions Hypoxia endothelium

endothelium-dependent relaxation of canine pulmonary artery endothelium after prolonged preservation

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Chinese Medical Journal 1998年第4期 43-46页

作者：朱彦林萍章张昭雄

Abstract Objective Experiments were designed to investigate the effect of Euro Collins (EC) solution and University of Wisconsin (UW) solution on function of pulmonary arterial endothelium. Methods Third order canine pulmonary artery segments were preserved in cold (4℃) UW (group 1, n=8) or EC (group 2, n=9) solutions for 16 hours. The preserved (group 1 and 2) and control (group 3, n=7) pulmonary arterial segments with and without endothelium were studied in vitro in organ chambers to measure isometric tension. Results The endothelium dependent relaxation to acetylcholine and adenosine diphosphate of group 1 and 3 were significantly better than those of group 2. Conclusions We concluded that endothelium dependent relaxation of canine pulmonary arterial endothelium to receptor dependent acetylcholine and adenosine diphosphate were impaired after preservation with Euro Collins solution. However, endothelium dependent relaxation of pulmonary segments were well maintained after preservation with University of Wisconsin solution.

关键词：林萍朱彦 artery pulmonary endothelium canine relaxation endothelium-dependent

Effect of Captopril on Antithrombus Function of endothelium

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Journal of Huazhong University of Science and Technology(Medical Sciences) 1995年第4期15卷 217-219页

作者：熊一力赵华月 Department of Medicine Tongji Hospital Tongji Medical University Wuhan

The experimental models of cultured porcine aortic endothelial cells(EC) in vitro were established. 6-keto-prostaglandin F1a(6-keto-PGF1a), thromboxane B2(TXB2) content, plasminogen activator(P A), plasminogen activator inhibitor(PAI) activity in cultured medium and cyclic adenosine monophosphate(cAMP) level in EC were measured with radioimmunoassay (RIA), chromogenic substrates methods, in order to assess the effect and mechanism of captopril(CP) on antithrombus function of EC. The results showed that after administration of CP, the contents of 6-keto-PGF1a and cAMP and PA activity were significantly higher, PAI activity were remarkably lower than those of control group. These effects were dose-dependent. Our finding indicated that CP might act as a prospective drug for antithrombosis through promoting anticoagulation and fibrinolysis function and increasing antithrombus action of EC.

关键词： captopril endothelium cultured cell

RBC aggregation,deformation and adhesion to endothelium:Role of nitric oxide derived from L-Arginine and sodium nitroprusside

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Journal of Innovative Optical Health Sciences 2024年第5期17卷 53-65页

作者： M.K.Maksimov P.B.Ermolinskiy O.N.Scheglovitova N.N.Sklyankina A.V.Muravyov A.E.Lugovtsov A.V.Priezzhev Faculty of Physics M.V.Lomonosov Moscow State University bld.1subbuilding.2Leninskie goryMoscow 11991Russia N.F.Gamaleya National Research Center for Epidemiology and Microbiology 18 Gamaleya StreetMoscow 123098Russia K.D.Ushinsky Yaroslavl State Pedagogical University 108/1 Respublikanskaya StreetYaroslavl 150000Russia

Red blood cells(RBCs)are the most abundant human blood *** aggregation and deformation strongly determine blood viscosity which impacts hemorheology and *** turn,RBC properties depend on di®erent endogenous and exogenous *** such factor is nitric oxide(NO),which is mainly produced by endothelial cells(EC)from L-arginine amino acid in the circulatory *** the mechanisms of the RBC-endothelium interplay are not clear up to date and considering its possible clinical importance,the aims of this study are to investigate in vitro:(1)The effect of L-arginine induced NO on RBC aggregation and adhesion to endothelium;(2)the NO e®ect on RBC aggregation and deformation induced by L-arginine and sodium nitroprusside without the presence of endothelium in the *** RBC aggregation and adhesion to a monolayer of EC were studied using optical tweezers(OT).The RBC deformability and aggregation without endothelium in the samples were studied using the flow chamber method and Myrenne *** confirmed that NO increases deformability and decreases aggregation of *** showed that the soluble guanylate cyclase pathway appears to be the only NO signaling pathway *** the samples with the endothelium,the "bell-shaped"dependence of RBC aggregation force on L-arginine concentration was observed,which improves our knowledge about the process of NO production by ***,data related to L-arginine accumulation by endothelium were obtained:Necessity of the presence of extracellular L-arginine stated by other authors was put under *** our study,NO decreased the RBC-endothelium adhesion,however,the tendency appeared to be weak and was not confirmed in another set of *** our knowledge,this is the first attempt to measure the forces of RBC adhesion to endothelium monolayer with OT.

关键词： Red blood cells aggregation L-arginine endothelium optical tweezers Myrenne flow chamber

endothelium-derived essential signals involved in pancreas organogenesis

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World Journal of Experimental Medicine 2015年第2期5卷 40-49页

作者： Dodanim Talavera-Adame Donald C Dafoe Comprehensive Transplant Center Department of Surgery Cedars-Sinai Medical Center Board of Governors Regenerative Medicine Institute Cedars-Sinai Medical Center

Endothelial cells(ECs) are essential for pancreas differentiation, endocrine specification, and endocrine function. They are also involved in the physiopathology of type 1 and type 2 diabetes. During embryogenesis, aortic ECs provide specific factors that maintain the expression of key genes for pancreas development such as pancreatic and duodenal homeobox-1. Other unknown factors are also important for pancreatic endocrine specification and formation of insulin-producing beta cells. Endocrine precursors proliferate interspersed with ductal cells and exocrine precursors and, at some point of development, these endocrine precursors migrate to pancreatic mesenchyme and start forming the islets of Langerhans. By the end of the gestation and close to birth, these islets contain immature beta cells with the capacity to express vascular endothelial growth factor and therefore to recruit ECs from the surrounding microenvironment. ECs in turn produce factors that are essential to maintain insulin secretion in pancreatic beta cells. Once assembled, a cross talk between endocrine cells and ECs maintain the integrity of islets toward an adequate function during the whole life of the adult individual. This review will focus in the EC role in the differentiation and maturation of pancreatic beta cells during embryogenesis as well as the current knowledge about the involvement of endothelium to derive pancreatic beta cells in vitro from mouse or human pluripotent stem cells.

关键词： endothelium endothelium-derived signals Differentiation Pancreas development Organogenesis