scholarly journals Experimental Renovascular Disease Induces Endothelial Cell Mitochondrial Damage and Impairs Endothelium-Dependent Relaxation of Renal Artery Segments

2020 ◽  
Vol 33 (8) ◽  
pp. 765-774
Author(s):  
Arash Aghajani Nargesi ◽  
Xiang-Yang Zhu ◽  
Ishran M Saadiq ◽  
Kyra L Jordan ◽  
Amir Lerman ◽  
...  
Keyword(s):  
Endothelial Cell ◽  
Renal Artery ◽  
Tube Formation ◽  
Mitochondrial Damage ◽  
In Vivo Studies ◽  
Mitochondrial Morphology ◽  
Renovascular Disease ◽  
And Function

Abstract BACKGROUND Mitochondria modulate endothelial cell (EC) function, but may be damaged during renal disease. We hypothesized that the ischemic and metabolic constituents of swine renovascular disease (RVD) induce mitochondrial damage and impair the function of renal artery ECs. METHODS Pigs were studied after 16 weeks of metabolic syndrome (MetS), renal artery stenosis (RAS), or MetS + RAS, and Lean pigs served as control (n = 6 each). Mitochondrial morphology, homeostasis, and function were measured in isolated primary stenotic-kidney artery ECs. EC functions were assessed in vitro, whereas vasoreactivity of renal artery segments was characterized in organ baths. RESULTS Lean + RAS and MetS + RAS ECs showed increased mitochondrial area and decreased matrix density. Mitochondrial biogenesis was impaired in MetS and MetS + RAS compared with their respective controls. Mitochondrial membrane potential similarly decreased in MetS, Lean + RAS, and MetS + RAS groups, whereas production of reactive oxygen species increased in MetS vs. Lean, but further increased in both RAS groups. EC tube formation was impaired in MetS, RAS, and MetS + RAS vs. Lean, but EC proliferation and endothelial-dependent relaxation of renal artery segments were blunted in MetS vs. Lean, but further attenuated in Lean + RAS and MetS + RAS. CONCLUSIONS MetS and RAS damage mitochondria in pig renal artery ECs, which may impair EC function. Coexisting MetS and RAS did not aggravate EC mitochondrial damage in the short time of our in vivo studies, suggesting that mitochondrial injury is associated with impaired renal artery EC function.

scholarly journals The role of anti-endothelial cell antibodies in Kawasaki disease -in vitro and in vivo studies

2002 ◽  
Vol 130 (2) ◽  
pp. 233-240 ◽  
Author(s):  
E. GRUNEBAUM ◽  
M. BLANK ◽  
S. COHEN ◽  
A. AFEK ◽  
J. KOPOLOVIC ◽  
...  
Keyword(s):  
Endothelial Cell ◽  
Kawasaki Disease ◽  
In Vivo Studies

scholarly journals Alcohol-and-HIV-Induced Lysosomal Dysfunction Regulates Extracellular Vesicles Secretion in Vitro and in Liver-Humanized Mice

Biology ◽  
2021 ◽  
Vol 10 (1) ◽  
pp. 29
Author(s):  
Raghubendra Singh Dagur ◽  
Moses New-Aaron ◽  
Murali Ganesan ◽  
Weimin Wang ◽  
Svetlana Romanova ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Extracellular Vesicles ◽  
Treated Group ◽  
Human Hepatocytes ◽  
In Vivo Studies ◽  
People Living With Hiv ◽  
Humanized Mouse Model ◽  
And Function

Background: Alcohol abuse is common in people living with HIV-1 and dramaticallyenhances the severity of HIV-induced liver damage by inducing oxidative stress and lysosomaldysfunction in the liver cells. We hypothesize that the increased release of extracellular vesicles(EVs) in hepatocytes and liver humanized mouse model is linked to lysosome dysfunction. Methods:The study was performed on primary human hepatocytes and human hepatoma RLWXP-GFP (Huh7.5 cells stably transfected with CYP2E1 and XPack-GFP) cells and validated on ethanol-fed liverhumanizedfumarylacetoacetate hydrolase (Fah)-/-, Rag2-/-, common cytokine receptor gamma chainknockout (FRG-KO) mice. Cells and mice were infected with HIV-1ADA virus. Results: We observedan increase in the secretion of EVs associated with a decrease in lysosomal activity and expressionof lysosomal-associated membrane protein 1. Next-generation RNA sequencing of primary humanhepatocytes revealed 63 differentially expressed genes, with 13 downregulated and 50 upregulatedgenes in the alcohol–HIV-treated group. Upstream regulator analysis of differentially expressedgenes through Ingenuity Pathway Analysis identified transcriptional regulators affecting downstreamgenes associated with increased oxidative stress, lysosomal associated disease, and function andEVs biogenesis. Our in vitro findings were corroborated by in vivo studies on human hepatocytetransplantedhumanized mice, indicating that intensive EVs’ generation by human hepatocytes andtheir secretion to serum was associated with increased oxidative stress and reduction in lysosomalactivities triggered by HIV infection and ethanol diet. Conclusion: HIV-and-ethanol-metabolisminducedEVs release is tightly controlled by lysosome status in hepatocytes and participates in thedevelopment of double-insult-induced liver injury.

Abstract 186: Hdac7-derived 7aa Peptide May Function as a Phosphorylation Carrier

2016 ◽  
Vol 36 (suppl_1) ◽  
Author(s):  
Junyao Yang ◽  
Wen Wang ◽  
Qian Wang ◽  
Lingfang Zeng
Keyword(s):  
Endothelial Cell ◽  
Vascular Endothelial Cell ◽  
Blood Perfusion ◽  
Open Reading Frames ◽  
In Vivo Studies ◽  
Buffer System ◽  
Vascular Progenitor Cells ◽  
Upstream Kinase

Background: Histone deacetylase 7 (HDAC7) belongs to class II HDAC family, playing a pivotal role in the maintenance of endothelium integrity. There are 8 splicing variants in mouse HDAC7 mRNAs. Within the 5’ terminal non-coding area of some variants, there exist some short open reading frames (sORFs). Whether these sORFs can be translated and their potential roles in cellular physiology remain unclear. Method and results: Our previous studies suggested that one mouse HDAC7 produced a 7aa peptide from the non-coding area. In this study, we demonstrated that one sORF encoding a 7 amino acids (aa)-peptide could be translated in response to vascular endothelial cell growth factor (VEGF) in vascular progenitor cells (VPCs). The 7aa-peptide (7A) could be phosphorylated at serine residue via MEKK1. Importantly, the phosphorylated 7aa-peptide (7Ap) could transfer the phosphorylation group to the Thr residue of the 14-3-3γ protein in a cell free in-gel buffer system. The in vitro functional analyses revealed that 7A enhanced VEGF-induced VPC migration and differentiation toward endothelial cell (EC) lineage, in which MEKK1 and 14-3-3γ served as upstream kinase and downstream effector respectively. Knockdown of either MEKK1 or 14-3-3γ attenuated VEGF-induced VPC migration and differentiation. Exogenous 7Ap could rescue VEGF effect in MEKK1 but not in 14-3-3γ knockdown cells. The in vivo studies showed that 7A especially 7Ap induced capillary vessel formation within matrigel plug assays, increased re-endothelialization and suppressed neointima formation in the femoral artery injury model, and promoted the foot blood perfusion recovery in the hindlimb ischemia model. Conclusion: These results indicate that the sORFs within the non-coding area can be translated under some circumstances and that the 7aa-peptide may play an important role in cellular processes like migration and differentiation via acting as a phosphorylation carrier. Significance: As a phosphorylation carrier, 7aa possesses therapeutic potentials in tackling angiogenesis related diseases.

Abstract 11: Thioredoxin-Interacting Protein Is Required for VEGF-Induced Angiogenesis Through Regulation of VEGFR2 Internalization

2012 ◽  
Vol 32 (suppl_1) ◽  
Author(s):  
Shin-Young Park ◽  
Chen Yan ◽  
Bradford C Berk
Keyword(s):  
Umbilical Vein ◽  
Fold Increase ◽  
Tube Formation ◽  
In Vivo Studies ◽  
Vegf Receptor ◽  
Cell Fractionation ◽  
Interacting Protein ◽  
Thioredoxin Interacting Protein

Introduction— Thioredoxin-interacting protein (TXNIP) is an arrestin-like scaffold protein. We have shown previously that it is necessary for the transactivation of the vascular endothelial growth factor (VEGF) receptor 2 (VEGFR2) as well as promoting the migration and survival of endothelial cells (ECs). However, its roles in VEGF-induced angiogenesis and in vivo studies of TXNIP function have not been elucidated. Hypothesis— TXNIP regulates VEGF-mediated angiogenesis through modulation of angiogenic signaling pathways in ECs. Methods and Results— To determine the functions of TXNIP in ECs, we generated endothelial-specific TXNIP knockout (EC-TXNIP KO) mice (TXNIPflox/flox: Tie2-Cre/+). These mice displayed impaired capillary growth of the retinal vasculature compared to control mice. Furthermore, aortic rings from EC-TXNIP KO mice exhibited fewer and shorter vascular sprouts than those in control mice. To investigate the role of TXNIP in the regulation of VEGF-induced angiogenesis, we determined the subcellular localization of TXNIP in human umbilical vein EC (HUVEC). Immunofluorescence and cell fractionation studies revealed that upon VEGF stimulation (10ng/ml). TXNIP translocated from cytoplasm to the plasma membrane. There was a 9 fold increase of membrane associated TXNIP with a peak at 15 minutes compared to non-VEGF treatment cells. We hypothesized that membrane associated TXNIP may modulate VEGFR2 internalization and thereby affect VEGF-induced signaling and angiogenesis. To investigate this, we performed in vitro cell surface biotinylation assays in HUVEC. VEGFR2 internalization was decreased by 65% in TXNIP siRNA knockdown cells compared to control siRNA treated cells following VEGF stimulation. Consistent with this result, VEGF-induced phosphorylation of VEGFR2, PLCγ and ERK1/2 was decreased by knockdown of TXNIP. Significantly, TXNIP knockdown inhibited VEGF-induced proliferation and tube formation in vitro. Conclusion— Our results suggest that TXNIP can modulate VEGF-induced angiogenesis and signaling by regulation of VEGFR2 internalization.

scholarly journals Cardioprotective Activity of Selected Polyphenols Based on Epithelial and Aortic Cell Lines. A Review

Molecules ◽  
2020 ◽  
Vol 25 (22) ◽  
pp. 5343
Author(s):  
Michał Otręba ◽  
Leon Kośmider ◽  
Jerzy Stojko ◽  
Anna Rzepecka-Stojko
Keyword(s):  
Endothelial Cells ◽  
Tube Formation ◽  
Health Claims ◽  
In Vivo Studies ◽  
Positive Effects ◽  
Endothelial Tube Formation ◽  
Disease Therapy ◽  
Species Production

Polyphenols have recently gained popularity among the general public as products and diets classified as healthy and containing naturally occurring phenols. Many polyphenolic extracts are available on the market as dietary supplements, functional foods, or cosmetics, taking advantage of clients’ desire to live a healthier and longer life. However, due to the difficulty of discovering the in vivo functions of polyphenols, most of the research focuses on in vitro studies. In this review, we focused on the cardioprotective activity of different polyphenols as possible candidates for use in cardiovascular disease therapy and for improving the quality of life of patients. Thus, the studies, which were mainly based on endothelial cells, aortic cells, and some in vivo studies, were analyzed. Based on the reviewed articles, polyphenols have a few points of action, including inhibition of acetylcholinesterase, decrease in reactive oxygen species production and endothelial tube formation, stimulation of acetylcholine-induced endothelium-derived mediator release, and others, which lead to their cardio- and/or vasoprotective effects on endothelial cells. The obtained results suggest positive effects of polyphenols, but more long-term in vivo studies demonstrating effects on mechanism of action, sensitivity, and specificity or efficacy are needed before legal health claims can be made.

Ethanol enhances leukocyte-endothelial cell interactions in mesenteric venules

1990 ◽  
Vol 259 (4) ◽  
pp. G578-G583 ◽  
Author(s):  
P. R. Kvietys ◽  
M. A. Perry ◽  
T. S. Gaginella ◽  
D. N. Granger
Keyword(s):  
Endothelial Cell ◽  
Receptor Antagonist ◽  
Alcohol Intoxication ◽  
Leukotriene B4 ◽  
Cell Interactions ◽  
In Vivo Studies ◽  
Rolling Velocity ◽  
Neutrophil Adherence

In vivo studies have implicated neutrophils in the gastric mucosal injury produced by intraluminal administration of ethanol. However, in vitro studies indicate that ethanol inhibits various neutrophil functions such as adherence, chemotaxis, and degranulation. The aim of the present study was to assess whether ethanol, at clinically relevant concentrations, is proinflammatory in vivo. Ethanol (0.2, 1.0, 2.0, and 4.0%) was applied to the surface of the cat mesentery, and neutrophil adherence to venules (30 microns diam) and extravasation into the interstitium were quantitated using intravital microscopy. Hemodynamic parameters were also measured (venular diameter, red blood cell velocity, and leukocyte rolling velocity) or calculated (venular blood flow and wall shear stress). In this model ethanol produced a dose-dependent increase in neutrophil adherence and extravasation. The increase in leukocyte-endothelial cell interactions could not be attributed to alterations in hemodynamic factors. Pretreatment of animals with a monoclonal antibody (MoAb IB4) directed to the neutrophil CD11/CD18 adherence complex completely prevented the ethanol-induced neutrophil adherence and extravasation. Pretreatment with a leukotriene B4 (LTB4)-receptor antagonist (SC 41930) or a platelet-activating factor (PAF)-receptor antagonist (WEB 2170) did not alter the ethanol-induced neutrophil-endothelial interactions. We conclude that ethanol is proinflammatory at concentrations which may be achieved in the mucosal interstitium during acute alcohol intoxication. The ethanol-induced leukocyte adherence and extravasation is dependent on the expression of adhesive glycoproteins. The inflammatory mediators, PAF and LTB4, do not appear to play an important role in the leukocyte-endothelial cell interactions initiated by ethanol.

CYLD regulates angiogenesis by mediating vascular endothelial cell migration

Blood ◽  
2010 ◽  
Vol 115 (20) ◽  
pp. 4130-4137 ◽  
Author(s):  
Jinmin Gao ◽  
Lei Sun ◽  
Lihong Huo ◽  
Min Liu ◽  
Dengwen Li ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Cell Migration ◽  
Endothelial Cell ◽  
Vascular Endothelial Cells ◽  
Vascular Endothelial Cell ◽  
Tube Formation ◽  
Endothelial Cell Migration ◽  
Vascular Endothelial

Cylindromatosis (CYLD) is a deubiquitinase that was initially identified as a tumor suppressor and has recently been implicated in diverse normal physiologic processes. In this study, we have investigated the involvement of CYLD in angiogenesis, the formation of new blood vessels from preexisting ones. We find that knockdown of CYLD expression significantly impairs angiogenesis in vitro in both matrigel-based tube formation assay and collagen-based 3-dimensional capillary sprouting assay. Disruption of CYLD also remarkably inhibits angiogenic response in vivo, as evidenced by diminished blood vessel growth into the angioreactors implanted in mice. Mechanistic studies show that CYLD regulates angiogenesis by mediating the spreading and migration of vascular endothelial cells. Silencing of CYLD dramatically decreases microtubule dynamics in endothelial cells and inhibits endothelial cell migration by blocking the polarization process. Furthermore, we identify Rac1 activation as an important factor contributing to the action of CYLD in regulating endothelial cell migration and angiogenesis. Our findings thus uncover a previously unrecognized role for CYLD in the angiogenic process and provide a novel mechanism for Rac1 activation during endothelial cell migration and angiogenesis.

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