Contributions of Microscopy to the Diagnosis and Investigation of Aids-Associated Renal Disease

Microscopy has had a major role in the analysis of renal disorders associated with human immunodeficiency virus (HIV) infection, both as a diagnostic method and as a means of studying pathogenic mechanisms. In the diagnostic realm, microscopic analysis of renal tissue obtained at biopsy and autopsy is a mainstay for the detection of a wide range of glomerular, vascular, and tubulointerstitial diseases. As an investigative tool, microscopy has made an important, albeit somewhat controversial, contribution to our understanding of the pathogenesis of at least one HIV-associated renal lesion.A variety of ultrastructural alterations have been documented in association with HIV infection. These include tubuloreticular inclusions (most commonly seen in vascular endothelial cells and mononuclear leukocytes)(Fig. la), cylindrical confronting cisternae (typically found in mononuclear leukocytes) (Fig. lb), and nuclear abnormalities such as nuclear bodies and granular change (most often in tubulointerstitial cells) (Fig. lc).

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Modeling the three-way feedback between cellular contractility, actin polymerization, and adhesion turnover resolves the contradictory effects of RhoA and Rac1 on endothelial junction dynamics

10.1101/2021.03.15.435512 ◽

2021 ◽

Author(s):

Eoin McEvoy ◽

Tal Sneh ◽

Emad Moeendarbary ◽

Gloria E Marino ◽

Xingyu Chen ◽

...

Keyword(s):

Actin Polymerization ◽

Vascular Endothelial Cells ◽

Vascular Endothelial ◽

Dynamic Rupture ◽

Modeling Framework ◽

Cell Contractility ◽

Wide Range ◽

Rho Family ◽

Rhoa Signaling ◽

Endothelial Junction

The formation and recovery of gaps in the vascular endothelium governs a wide range of physiological and pathological phenomena, from angiogenesis to atherosclerosis and tumor cell extravasation. However, the interplay between the mechanical and signaling processes that drive dynamic behavior in vascular endothelial cells is not well understood. In this study, we propose a chemo-mechanical model to investigate the maintenance of endothelial junctions as dependent on the crosstalk between actomyosin contractility, VE-cadherin bond turnover, and actin polymerization, which mediate the forces exerted on the cell-cell interface. Our theoretical model reveals that active cell tension can stabilize cadherin bonds within an adhesion, but excessive RhoA signaling can drive bond dissociation and junction failure. While Rac1-mediated actin polymerization aids gap closure, high levels of Rac1 may also facilitate junction weakening. Combining the modeling framework with novel experiments, we identify how dynamic rupture and heal cycles emerge and, further, describe why gaps tend to localize at multi-cell contacts. Beyond, our analysis also indicates that a critical balance between RhoA and Rac1 expression is required to maintain junction stability and limit endothelial dysfunction. The model predicts how pharmacological modulation of actin polymerization and cell contractility impacts junction stability, with predictions subsequently validated experimentally. Our proposed framework can help guide the development of therapeutics that target the Rho family of GTPases and downstream active mechanical processes.

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An In Vitro Model of Diabetic Retinal Vascular Endothelial Dysfunction and Neuroretinal Degeneration

Journal of Diabetes Research ◽

10.1155/2021/9765119 ◽

2021 ◽

Vol 2021 ◽

pp. 1-12

Author(s):

Qiyun Wang ◽

Xinyuan Zhang ◽

Kaiyue Wang ◽

Ling Zhu ◽

Bingjie Qiu ◽

...

Keyword(s):

Cell Proliferation ◽

Endothelial Dysfunction ◽

Vascular Endothelial Cells ◽

Tube Formation ◽

Cell Counting ◽

Vascular Endothelial ◽

Migration Assay ◽

Tube Formation Assay ◽

Wide Range

Background. Diabetic retinopathy (DR) is a leading cause of blindness in working-age populations. Proper in vitro DR models are crucial for exploring pathophysiology and identifying novel therapeutic targets. This study establishes a rational in vitro diabetic retinal neuronal-endothelial dysfunction model and a comprehensive downstream validation system. Methods. Human retinal vascular endothelial cells (HRMECs) and retinal ganglion cells (RGCs) were treated with different glucose concentrations with mannitol as matched osmotic controls. Cell proliferation and viability were evaluated by the Cell Counting Kit-8. Cell migration was measured using a transwell migration assay. Cell sprouting was assessed by a tube formation assay. The VEGF expression was assessed by ELISA. RGCs were labeled by neurons and RGC markers TUJ1 and BRN3A for quantitative and morphological analysis. Apoptosis was detected using PI/Hoechst staining and TUNEL assay and quantified by ImageJ. Results. Cell proliferation and migration in HRMECs were significantly higher in the 25 mM glucose-treated group ( p < 0.001 ) but lower in the 50 mM and 100 mM groups ( p < 0.001 ). The permeability and the apoptotic index in HRMECs were statistically higher in the 25 mM, 50 mM, and 100 mM groups ( p < 0.05 ). The tube formation assay found that all the parameters were significantly higher in the 25 mM and 50 mM groups ( p < 0.001 ) concomitant with the elevated VEGFA expression in HRMECs ( p = 0.016 ). Cell viability was significantly lower in the 50 mM, 100 mM, and 150 mM groups in RGCs ( p 50 mM = 0.013 , p 100 mM = 0.019 , and p 150 mM = 0.002 ). Apoptosis was significantly elevated, but the proportion of RGCs with neurite extension was significantly lower in the 50 mM, 100 mM, and 150 mM groups ( p 50 mM < 0.001 , p 100 m M < 0.001 , and p 150 mM < 0.001 ). Conclusions. We have optimized glucose concentrations to model diabetic retinal endothelial (25-50 mM) or neuronal (50-100 mM) dysfunction in vitro, which have a wide range of downstream applications.

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CD147 (BSG) but not ACE2 expression is detectable in vascular endothelial cells within single cell RNA sequencing datasets derived from multiple tissues in healthy individuals

10.1101/2020.05.29.123513 ◽

2020 ◽

Cited By ~ 3

Author(s):

C Ganier ◽

X Du-Harpur ◽

N Harun ◽

B Wan ◽

C Arthurs ◽

...

Keyword(s):

Endothelial Cells ◽

Single Cell ◽

Vascular Endothelial Cells ◽

Cell Surface Receptor ◽

Vascular Endothelial ◽

Healthy Individuals ◽

Sequencing Data ◽

Direct Role ◽

Single Cell Sequencing ◽

Wide Range

ABSTRACTCoronavirus disease 2019 (COVID-19) is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and is associated with a wide range of systemic manifestations. Several observations support a role for vascular endothelial dysfunction in the pathogenesis including an increased incidence of thrombotic events and coagulopathy and the presence of vascular risk factors as an independent predictor of poor prognosis. It has recently been reported that endothelitis is associated with viral inclusion bodies suggesting a direct role for SARS-CoV-2 in the pathogenesis. The ACE2 receptor has been shown to mediate SARS-CoV-2 uptake and it has been proposed that CD147 (BSG) can function as an alternative cell surface receptor. To define the endothelial cell populations that are susceptible to infection with SARS-CoV-2, we investigated the expression of ACE2 as well as other genes implicated in the cellular entry of SARS-Cov-2 in the vascular endothelium through the analysis of single cell sequencing data derived from multiple human tissues (skin, liver, kidney, lung and intestine). We found that CD147 (BSG) but not ACE2 is detectable in vascular endothelial cells within single cell sequencing datasets derived from multiple tissues in healthy individuals. This implies that either ACE2 is not expressed in healthy tissue but is instead induced in response to SARS-Cov2 or that SARS-Cov2 enters endothelial cells via an alternative receptor such as CD147.

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An E-selectin targeting and MMP-2-responsive dextran–curcumin polymeric prodrug for targeted therapy of acute kidney injury

Biomaterials Science ◽

10.1039/c8bm00813b ◽

2018 ◽

Vol 6 (12) ◽

pp. 3397-3409 ◽

Cited By ~ 5

Author(s):

Jing-Bo Hu ◽

Di Liu ◽

Jing Qi ◽

Kong-jun Lu ◽

Fei-yang Jin ◽

...

Keyword(s):

Acute Kidney Injury ◽

Endothelial Cells ◽

Targeted Therapy ◽

Vascular Endothelial Cells ◽

Kidney Injury ◽

Renal Tissue ◽

Matrix Metalloproteinase 2 ◽

Vascular Endothelial ◽

Therapeutic Outcomes ◽

Polymeric Prodrug

Based on the overproduction of matrix metalloproteinase-2 (MMP-2) in renal tissue during acute kidney injury (AKI) occurrence, we developed a MMP-2 enzyme-triggered polymeric prodrug with sialic acid (SA) as the targeting group to the inflamed vascular endothelial cells for enhanced therapeutic outcomes.

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Functional transport of organic anions and cations in the murine mesonephros

AJP Renal Physiology ◽

10.1152/ajprenal.00021.2018 ◽

2018 ◽

Vol 315 (1) ◽

pp. F130-F137 ◽

Cited By ~ 4

Author(s):

Melanie L. Lawrence ◽

James R. Smith ◽

Jamie A. Davies

Keyword(s):

Vascular Endothelial Cells ◽

Functional Characterization ◽

Renal Tissue ◽

Organic Anions ◽

Vascular Endothelial ◽

Hematopoietic Stem ◽

Excretory Function ◽

Renal Structure ◽

Anions And Cations

The mesonephros of mammals is a transient renal structure that contributes to various aspects of mammalian fetal development, including the male reproductive system, hematopoietic stem cells, and vascular endothelial cells. The mesonephros develops from the intermediate mesoderm and forms tubules that are segmented in a similar way to the nephrons of the permanent kidney (but lacking loops of Henle). Early studies have suggested that the mesonephros in marsupials and some placental mammals may perform an excretory function, but these studies have not directly shown active transport of organic anions and cations. Excretory function in the rodent mesonephros has not been investigated. Functional characterization of the earliest stages of mammalian renal development is important for our understanding of congenital disease and may help to inform the growing field of renal tissue engineering. Here, we use live uptake and efflux assays in vitro to show that the murine mesonephros is able to transport organic anions and cations through specific transporters from early in its development. Transcript analysis suggests that there are subtle differences between the transporters involved in uptake and efflux by the murine permanent metanephric tubules and by the mesonephric tubules. These data suggest that the mammalian mesonephros can provide an excretory function for the early developing embryo, in addition to the excretory function provided by the placenta.

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M.629 Homocysteine inhibits lysyl oxidase (LOX) and downregulates LOX expression in vascular endothelial cells

Atherosclerosis ◽

10.1016/s0021-9150(04)90627-2 ◽

2004 ◽

Vol 5 (1) ◽

pp. 146

Author(s):

B RAPOSO

Keyword(s):

Endothelial Cells ◽

Vascular Endothelial Cells ◽

Lysyl Oxidase ◽

Vascular Endothelial

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Anti-metalloproteinase-9 Activities of Selected Indonesian Zingiberaceae Rhizome Extracts in Lipopolysaccharide-induced Human Vascular Endothelial Cells In Vitro

Planta Medica ◽

10.1055/s-0031-1282610 ◽

2011 ◽

Vol 77 (12) ◽

Author(s):

Y Yanti ◽

N Steven ◽

A Wiharja ◽

S Fajarianto

Keyword(s):

Endothelial Cells ◽

Vascular Endothelial Cells ◽

Vascular Endothelial ◽

Metalloproteinase 9

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The Endothelial Cell and the Factor VIII Bypassing Activity of Prothrombin Complex Concentrate

Thrombosis and Haemostasis ◽

10.1055/s-0038-1647034 ◽

1988 ◽

Vol 60 (02) ◽

pp. 226-229 ◽

Cited By ~ 2

Author(s):

Jerome M Teitel ◽

Hong-Yu Ni ◽

John J Freedman ◽

M Bernadette Garvey

Keyword(s):

Endothelial Cells ◽

Endothelial Cell ◽

Factor Viii ◽

Prothrombin Complex Concentrate ◽

Vascular Endothelial Cells ◽

Vascular Endothelial ◽

Monolayer Cultures ◽

Coagulant Activity ◽

Time Courses ◽

Privileged Site

SummarySome classical hemophiliacs have a paradoxical hemostatic response to prothrombin complex concentrate (PCC). We hypothesized that vascular endothelial cells (EC) may contribute to this “factor VIII bypassing activity”. When PCC were incubated with suspensions or monolayer cultures of EC, they acquired the ability to partially bypass the defect of factor VIII deficient plasma. This factor VIII bypassing activity distributed with EC and not with the supernatant PCC, and was not a general property of intravascular cells. The effect of PCC was even more dramatic on fixed EC monolayers, which became procoagulant after incubation with PCC. The time courses of association and dissociation of the PCC-derived factor VIII bypassing activity of fixed and viable EC monolayers were both rapid. We conclude that EC may provide a privileged site for sequestration of constituents of PCC which express coagulant activity and which bypass the abnormality of factor VIII deficient plasma.

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Alterations in Vascular Endothelial Cell-related Plasma Proteins In Thalassaemic Patients and their Correlation with Clinical Symptoms

Thrombosis and Haemostasis ◽

10.1055/s-0038-1649879 ◽

1995 ◽

Vol 74 (04) ◽

pp. 1045-1049 ◽

Cited By ~ 38

Author(s):

P Butthep ◽

A Bunyaratvej ◽

Y Funahara ◽

H Kitaguchi ◽

S Fucharoen ◽

...

Keyword(s):

Endothelial Cells ◽

Endothelial Cell ◽

Immunosorbent Assay ◽

Plasma Proteins ◽

Clinical Symptoms ◽

Vascular Endothelial Cells ◽

Vascular Endothelial Cell ◽

Enzyme Linked Immunosorbent Assay ◽

Vascular Endothelial ◽

Leg Ulcers

SummaryAn increased level of plasma thrombomodulin (TM) in α- and β- thalassaemia was demonstrated using an enzyme-linked immunosorbent assay (ELISA). Nonsplenectomized patients with β-thalassaemia/ haemoglobin E (BE) had higher levels of TM than splenectomized cases (BE-S). Patients with leg ulcers (BE-LU) were found to have the highest increase in TM level. Appearance of larger platelets in all types of thalassaemic blood was observed indicating an increase in the number of younger platelets. These data indicate that injury of vascular endothelial cells is present in thalassaemic patients.

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