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Neutrophil-derived heparin binding protein triggers vascular leakage and synergizes with myeloperoxidase at the early stage of severe burns(With video)

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Burns & Trauma 2021年第1期9卷 240-254页

作者： Lu Liu Yiming Shao Yixuan Zhang Yunxi Yang Jiamin Huang Linbin Li Ran Sun Yuying Zhou Yicheng Su Bingwei Sun School of Medicine Jiangsu UniversityZhenjiang 212001Jiangsu ProvinceChina Department of Burns and Plastic Surgery Affiliated Suzhou Hospital of Nanjing Medical UniversitySuzhou 215002Jiangsu ProvinceChina

Background:Burn shock caused by vascular leakage is one of the main causes of high mortality in severe burn ***,the pathophysiological mechanism of vascular leakage is still *** purpose of this study was to explore the molecular mechanism of vascular leakage in the early stage of severe burn and provide a new target for the treatment of severe ***:Neutrophils were isolated from human peripheral blood by magnetic beads *** was used to detect neutrophil-derived granule proteins and glycocalyx injury products in *** vascular leakage and neutrophil movement were assessed by in vivo laser confocal imaging in mice,and high-quality video were ***-related molecules were investigated by *** damage to glycocalyx of mice vascular endothelial cellswas observed by transmission electron microscope and scanning electron *** analysis,flow cytometry and immunofluorescence were used to further study the relationship between human peripheral blood neutrophil-derived hypochlorite(HOCl)and CD44 of human vascular endothelial ***:In this study,we found that rapidly increasing activated neutrophils secrete heparin binding protein(HBP)andmyeloperoxidase(MPO)after severe burn *** HBP triggers vascular leakage with synergy of MPO,results in systemic edema and burn ***,we found that the MPO catalytic product HOCl but not MPO triggers CD44 extracellular domain shedding from vascular endothelial cells to damage the *** to the glycocalyx results in firm adhesion of neutrophils and increases vascular ***,MPO inhibitors partially protect the glycocalyx of vascular endothelial *** combination of HBP and MPO inhibitors markedly reduces vascular leakage and systemic edema in the early stage of severe ***:Taken together,these data reveal that neutrophil-derived HBP and MPO play an important synergies role in triggering vascular leakage a

关键词： Severe burn Heparin binding protein Myeloperoxidase vascular leakage Glycocalyx

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Aqueous angiopoietin-like levels correlate with optical coherence tomography angiography metrics in diabetic macular edema

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International Journal of Ophthalmology(English edition) 2021年第12期14卷 1888-1894页

作者： Jie Yan Wu-Jun Li Ya-Zhou Qin Xuan-Yu Qiu Li Qin Jing-Ming Li Department of Ophthalmology the First Affiliated Hospital of Xi’an Jiaotong UniversityXi’an 710061Shaanxi ProvinceChina Department of Ophthalmology Yulin Hospital of Traditional Chinese MedicineYulin 719000Shaanxi ProvinceChina

AIM:To quantitatively detect aqueous levels of angiopoietin-like(ANGPTL)3,ANGPTL4,and ANGPTL6 and investigate their correlation with optical coherence tomography angiography(OCTA)findings in patients with diabetic macular edema(DME).METHODS:This cross-sectional study included 23 patients(27 eyes)with type 2 diabetes and 16 control subjects(20 eyes).All patients underwent OCTA imaging and ultra-wide field fundus *** patients were categorized into two groups according to the presence or absence of diabetic retinopathy(DME group,14 patients,16 eyes);and non-diabetic retinopathy(NDR)group,9 patients,11 eyes,*** levels of ANGPTL3,ANGPTL4,and ANGPTL6 were assessed using suspension array technology,and foveal-centered 3×3 mm2 OCTA scans were automatically graded to determine the central,inner,and full vessel density(CVD,IVD,FVD);central,inner,and full perfusion density(CPD,IPD,FPD),foveal avascular zone(FAZ)area,FAZ perimeter,and FAZ circularity index(FAZ-CI)on superficial capillary ***,central subfield thickness(CST),cube volume(CV),and cube average thickness(CAT)were measured in a model of macular cube 512×***:Aqueous ANGPTL3 levels were not significantly different among the three groups(P>0.05).ANGPTL4 levels were significantly higher in the DME group than the control and NDR groups(Pvascular leakage in DME and may represent good targets for DME *** addition,OCT

关键词： diabetic retinopathy diabetic macular edema optical coherence tomography angiography angiopoietin-like vascular leakage

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Knockdown of fibrillin-1 suppresses retina-blood barrier dysfunction by inhibiting vascular endothelial apoptosis under diabetic conditions

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International Journal of Ophthalmology(English edition) 2024年第8期17卷 1403-1410页

作者： Yue Zhang Xiao-Jing Liu Xin-Ran Zhai Yao Yao Bin Shao Yu-Han Zhen Xin Zhang Zhe Xiao Li-Fang Wang Ming-Lian Zhang Zhi-Min Chen Hebei Eye Hospital Provincial Key Laboratory of OphthalmologyHebei Provincial Clinical Research Center for Eye DiseasesXingtai 054001Hebei ProvinceChina Department of Ophthalmology Hebei Medical UniversityShijiazhuang 050011Hebei ProvinceChina

AIM:To investigate the effects of fibrillin-1(FBN1)deletion on the integrity of retina-blood barrier function and the apoptosis of vascular endothelial cells under diabetic ***:Streptozotocin(STZ)-induced diabetic mice were used to simulate the diabetic conditions of diabetic retinopathy(DR)patients,and FBN1 expression was detected in retinas from STZ-diabetic mice and *** the Gene Expression Omnibus(GEO)database,the GSE60436 dataset was selected to analyze FBN1 expressions in fibrovascular membranes from DR *** lentivirus to knock down FBN1 levels,vascular leakage and endothelial barrier integrity were detected by Evans blue vascular permeability assay,fluorescein fundus angiography(FFA)and immunofluorescence labeled with tight junction marker in *** glucose-induced monkey retinal vascular endothelial cells(RF/6A)were used to investigate effects of FBN1 on the cells in *** vascular endothelial barrier integrity and apoptosis were detected by trans-endothelial electrical resistance(TEER)assay and flow cytometry,***:FBN1 mRNA expression was increased in retinas of STZ-induced diabetic mice and fibrovascular membranes of DR patients(GSE60436 datasets)using RNA-seq ***,knocking down of FBN1 by lentivirus intravitreal injection significantly inhibited the vascular leakage compared to STZ-DR group by Evans blue vascular permeability assay and FFA *** of tight junction markers in STZ-DR mouse retinas were lower than those in the control group,and knocking down of FBN1 increased the tight junction *** vitro,30 mmol/L glucose could significantly inhibit viability of RF/6A cells,and FBN1 mRNA expression was increased under 30 mmol/L glucose ***-regulation of FBN1 reduced high glucose(HG)-stimulated retinal microvascular endothelial cell permeability,increased TEER,and inhibited RF/6A cell apoptosis in ***:The expression level of FBN1 increases in reti

关键词： diabetic retinopathy fibrillin-1 retinablood barrier vascular leakage vascular permeability apoptosis retinal vascular endothelial cells

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*** hypertension promotes early mitochondrial fragmentation in retinal endothelial cells in a mouse model of glaucoma

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Annals of Eye Science 2018年第1期 424-424页

作者： Jorge L.Cueva Vargas Yoko Ito Khalil Miloudi Ariel M.Wilson Christine Vande Velde Przemyslaw Sapieha Adriana Di Polo Department of Neuroscience University of Montreal Hospital Research Center(CR-CHUM)MontrealQuebecCanada Department of Biochemistry Maisonneuve-Rosemont Hospital Research CentreUniversity of MontrealMontrealQuebecCanada Department of Ophthalmology Maisonneuve-Rosemont Hospital Research CentreUniversity of MontrealMontrealQuebecCanada Department of Neuroscience McGill UniversityMontrealQuebecCanada

Background:Retinal endothelial cells are very active and contribute to the integrity of the neurovascular *** dysfunction has been proposed to contribute to the pathogenesis of ***,we evaluated the hypothesis that ocular hypertension triggers mitochondrial alterations in endothelial cells impairing the integrity of the blood retinal barrier(BRB).Methods:Ocular hypertension was induced by injection of magnetic microbeads into the anterior chamber of EndoMito-EGFP mice,a strain expressing green fluorescent protein selectively in the mitochondria of endothelial *** density,mitochondrial volume,and the number of mitochondrial components were quantified in 3D-reconstructed images from whole-mounted retinas using Imaris ***-related protein(DRP-1),mitofusin-2(MFN-2)and optic atrophy-1(OPA-1)expression were assessed by western blot analysis of enriched endothelial *** structure was evaluated by transmission electron microscopy(TEM)and oxygen consumption rate was monitored by Seahorse *** integrity of the BRB was evaluated by quantifying Evans blue ***:Our data demonstrate that two and three weeks after ocular hypertension induction,the total mitochondria volume in endothelial cells decreased from 0.140±0.002µm3 from non-injured retinas to 0.108±0.005 and 0.093±0.007µm3,respectively in glaucomatous eyes(mean±S.E.M,ANOVA,Pleakage in glaucomatous retinas(n=3-6/group).In additi

关键词： Glaucoma endothelial cells mitochondria vascular leakage

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