scholarly journals Syndecan-1 is overexpressed in human thoracic aneurysm but is dispensable for the disease progression in vivo

2021 ◽  
Author(s):  
Sara Zalghout ◽  
Sophie Vo ◽  
Veronique Arocas ◽  
Soumaya Jadoui ◽  
Eva Hamade ◽  
...  
Keyword(s):  
Mouse Model ◽  
Aortic Wall ◽  
Vascular Wall ◽  
Protective Role ◽  
Abdominal Aneurysm ◽  
Potential Implication ◽  
Elastin Degradation ◽  
Model Combining ◽  
Underlying Mechanisms

Glycosaminoglycans (GAGs) pooling has been considered since long as one of the histopathological characteristics defining thoracic aortic aneurysm (TAA) together with smooth muscle cells (SMCs) apoptosis and elastin fibers degradation. However, few information is provided about GAGs composition or potential implication in TAA pathology. Syndecan-1 (Sdc-1) is a heparan sulfate proteoglycan that is implicated in extracellular matrix (ECM) interaction and assembly, regulation of SMCs phenotype and various aspects of inflammation in the vascular wall. In the current work, the regulation of Sdc-1 protein was examined in human TAA by ELISA and immunohistochemistry. In addition, the role of Sdc-1 was evaluated in descending TAA in vivo using a mouse model combining both aortic wall weakening and hypertension. Our results showed that Sdc-1 protein is over expressed in human TAA aortas compared to healthy counterparts and that SMCs are the major cell type expressing Sdc-1. Similarly, in the mouse model used, Sdc-1 expression was increased in TAA aortas compared to healthy samples. Although its protective role against abdominal aneurysm has been reported, we observed that Sdc-1 was dispensable for TAA prevalence or rupture. In addition, Sdc-1 deficiency did not alter the extent of aortic wall dilatation, elastin degradation, collagen deposition, or leukocyte recruitment in our TAA model. These findings suggest that Sdc-1 could be a biomarker revealing TAA pathology. Future investigations could uncover the underlying mechanisms leading to Sdc-1 expression alteration in TAA.

Losartan Increases No Production from the Bovine Aortic Wall That is Stimulated by Angiotensin II

2003 ◽  
Vol 1 (3) ◽  
pp. 113-117 ◽  
Author(s):  
M. Myronidou ◽  
B. Kokkas ◽  
A. Kouyoumtzis ◽  
N. Gregoriadis ◽  
A. Lourbopoulos ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Angiotensin Ii ◽  
Aortic Wall ◽  
Vascular Wall ◽  
Protective Role ◽  
Normal Function ◽  
No Production ◽  
Chemical Inactivation

In these studies we investigated if losartan, an AT1- receptor blocker has any beneficial effect on NO production from the bovine aortic preparations in vitro while under stimulation from angiotensin II. Experiments were performed on intact specimens of bovine thoracic aorta, incubated in Dulbeco's MOD medium in a metabolic shaker for 24 hours under 95 % O2 and 5 % CO2 at a temperature of 37°C. We found that angiotensin II 1nM−10 μM does not exert any statistically significant action on NO production. On the contrary, angiotensin II 10nM increases the production of NO by 58.14 % (from 12.16 + 2.9 μm/l to 19.23 + 4.2 μm/l in the presence of losartan 1nM (P<0.05). Nitric oxide levels depend on both rate production and rate catabolism or chemical inactivation. Such an equilibrium is vital for the normal function of many systems including the cardiovascular one. The above results demonstrate that the blockade of AT1-receptors favors the biosynthesis of NO and indicate the protective role of losartan on the vascular wall.

scholarly journals Immunoglobulin Attenuates Streptokinase-Mediated Virulence inStreptococcus dysgalactiae Subspeciesequisimilis Necrotizing Fasciitis

2017 ◽  
Vol 217 (2) ◽  
pp. 270-279 ◽  
Author(s):  
Federica Andreoni ◽  
Fabio Ugolini ◽  
Nadia Keller ◽  
Andrina Neff ◽  
Victor Nizet ◽  
...  
Keyword(s):  
Mortality Rate ◽  
Mouse Model ◽  
Necrotizing Fasciitis ◽  
Protective Role ◽  
Specific Antibodies ◽  
Blocking Antibodies ◽  
First Time ◽  
Very High

Abstract Background Necrotizing fasciitis (NF) retains a very high mortality rate despite prompt and adequate antibiotic treatment and surgical debridement. Necrotizing fasciitis has recently been associated withStreptococcus dysgalactiae subspeciesequisimilis (SDSE). Methods We investigated the causes of a very severe clinical manifestation of SDSE-NF by assessing both host and pathogen factors. Results We found a lack of streptokinase-function blocking antibodies in the patient resulting in increased streptokinase-mediated fibrinolysis and bacterial spread. At the same time, the clinical SDSE isolate produced very high levels of streptokinase. Exogenous immunoglobulin Gs (ex-IgGs) efficiently blocked streptokinase-mediated fibrinolysis in vitro, indicating a protective role against the action of streptokinase. In vivo, SDSE infection severity was also attenuated by ex-IgGs in a NF mouse model. Conclusions These findings illustrate for the first time that the lack of specific antibodies against streptococcal virulence factors, such as streptokinase, may contribute to NF disease severity. This can be counteracted by ex-IgGs.

scholarly journals MicroRNA-139-3p Suppresses Tumor Growth and Metastasis in Hepatocellular Carcinoma by Repressing ANXA2R

2018 ◽  
Vol 26 (9) ◽  
pp. 1391-1399 ◽  
Author(s):  
Zeng Cheng Zou ◽  
Min Dai ◽  
Zeng Yin Huang ◽  
Yi Lu ◽  
He Ping Xie ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Cell Migration ◽  
Cell Growth ◽  
Mouse Model ◽  
Migration And Invasion ◽  
Tumor Growth And Metastasis ◽  
Underlying Mechanisms ◽  
Hcc Cells

The direct roles of miR-139-3p on hepatocellular carcinoma (HCC) cell growth and metastasis remain poorly understood. We attempted to demonstrate the regulatory role of miR-139-3p in HCC progression and its underlying mechanisms. Here we showed that miR-139-3p expression was significantly reduced in the HCC tissues compared to paratumor tissues. Exogenous overexpression of miR-139-3p inhibited the migration and invasion of HCC cells, whereas downregulation of miR-139-3p was able to induce HCC HepG2 and SNU-449 cell migration and invasion. In addition, miR-139-3p inhibited HCC growth and lung metastasis in an in vivo mouse model, which is mainly regulated by annexin A2 receptor (ANXA2R). Finally, we identified that the expression of miR-139-3p was inversely correlated with ANXA2R expression in human HCC tissue. All these results demonstrated that miR-139-3p inhibited the metastasis process in HCC by downregulating ANXA2R expression.

scholarly journals Role of Neutrophils in Response to Bordetella pertussis Infection in Mice

2008 ◽  
Vol 77 (3) ◽  
pp. 1182-1188 ◽  
Author(s):  
Charlotte Andreasen ◽  
Nicholas H. Carbonetti
Keyword(s):  
Mouse Model ◽  
Bacterial Growth ◽  
Bordetella Pertussis ◽  
Protective Role ◽  
In Vivo Studies ◽  
Target Cells ◽  
Pertussis Infection ◽  
Immune Mouse

ABSTRACT Pertussis is an acute respiratory disease caused by the bacterium Bordetella pertussis, for which humans are the only known reservoir. During infection, B. pertussis releases several toxins, including pertussis toxin (PT) and adenylate cyclase toxin (ACT), which have both been shown to play roles in promoting bacterial growth during early infection in a mouse model. Furthermore, in vitro and in vivo studies suggest that PT and ACT affect neutrophil chemotaxis and/or function, thereby altering the innate immune response. In this study we depleted animals of neutrophils to investigate whether neutrophils play a protective role during B. pertussis infection in mice. In addition, by infection with toxin-deficient strains, we investigated whether neutrophils are the main targets for PT and/or ACT activity in promoting bacterial growth. Surprisingly, we found no role for neutrophils during B. pertussis infection in naïve mice. However, in previously infected (immune) mice or in mice receiving immune serum, we observed a significant role for neutrophils during infection. Furthermore, in this immune mouse model our evidence indicates that neutrophils appear to be the main target cells for ACT, but not for PT.

VASCULAR CONNECTIVE TISSUE UNDER THE INFLUENCE OF THYROXINE

1961 ◽  
Vol 37 (2) ◽  
pp. 191-198 ◽  
Author(s):  
lb Lorenzen
Keyword(s):  
Connective Tissue ◽  
Microscopic Examination ◽  
Aortic Wall ◽  
Physiological Saline ◽  
Vascular Wall ◽  
Treated Group ◽  
Microscopic Appearance ◽  
Clear Cut ◽  
Hexosamine Content

ABSTRACT Aortae were studied in three groups of rabbits: First group: Injected with epinephrine for two weeks and with 1-thyroxine for another two weeks. Second group: Injected with epinephrine for two weeks and with physiological saline for another two weeks. Third group: Untreated controls. The aortae were assessed by gross and microscopic examination, and the content of water, hexosamine, hydroxyproline and calcium as well as the in vivo uptake of 35S sulphate determined. The alterations in the epinephrine-thyroxine-treated group were not so pronounced as previously observed after simultaneous injections of epinephrine plus 1-thyroxine. But the thyroxine injections in this group brought about a clear-cut increase in hexosamine content and 35S sulphate uptake as compared with the untreated controls. This presumably indicates that owing to the thyroxine treatment the vascular wall was still exposed to damage despite the discontinuation of the epinephrine injections. In contradistinction, the epinephrine-saline-treated rabbits did not differ significantly from the controls as regards biochemical changes in the aortic wall two weeks after discontinuation of epinephrine. When the microscopic appearance were also considered, this was interpreted as a sign of cessation of the injuries to the vascular wall and of healing.

scholarly journals Unique Human and Mouse β-cell Senescence-Associated Secretory Phenotype (SASP) Reveal Conserved Signaling Pathways and Heterogeneous Factors

2021 ◽  
Author(s):  
Ayush Midha ◽  
Hui Pan ◽  
Cristian Abarca ◽  
Joshua Andle ◽  
Priscila Carapeto ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Mouse Model ◽  
Cell Senescence ◽  
Cellular Stress Response ◽  
Matrix Remodeling ◽  
Β Cells ◽  
Β Cell ◽  
Potential Implication ◽  
Secretory Phenotype

The aging of pancreatic β-cells may undermine their ability to compensate for insulin resistance, leading to the development of type 2 diabetes (T2D). Aging β-cells acquire markers of cellular senescence and develop a senescence-associated secretory phenotype (SASP) that can lead to senescence and dysfunction of neighboring cells through paracrine actions, contributing to b-cell failure. Herein, we defined the β-cell SASP signature based on unbiased proteomic analysis of conditioned media of cells obtained from mouse and human senescent β-cells and a chemically-induced mouse model of DNA damage capable of inducing SASP. These experiments revealed that the β-cell SASP is enriched for factors associated with inflammation, cellular stress response, and extracellular matrix remodeling across species. Multiple SASP factors were transcriptionally upregulated in models of β-cell senescence, aging, insulin resistance and T2D. Single-cell transcriptomic analysis of islets from an <i>in vivo</i> mouse model of reversible insulin resistance indicated unique and partly reversible changes in β-cell subpopulations associated with senescence. Collectively, these results demonstrate the unique secretory profile of senescent b-cells and its potential implication in health and disease.

scholarly journals Neuronal Protective Role of PBEF in a Mouse Model of Cerebral Ischemia

2010 ◽  
Vol 30 (12) ◽  
pp. 1962-1971 ◽  
Author(s):  
Weiping Zhang ◽  
Yicheng Xie ◽  
Tiannan Wang ◽  
Jing Bi ◽  
Hailong Li ◽  
...  
Keyword(s):  
Cerebral Ischemia ◽  
Mouse Model ◽  
Infarct Volume ◽  
Protective Role ◽  
Wild Type ◽  
Nicotinamide Phosphoribosyltransferase ◽  
Fluoro Jade B ◽  
Rate Limiting

Pre-B-cell colony-enhancing factor (PBEF) (also known as nicotinamide phosphoribosyltransferase) is a rate-limiting enzyme in the salvage pathway for mammalian biosynthesis of nicotinamide adenine dinucleotide (NAD+). By synthesizing NAD+, PBEF functions to maintain an energy supply that has critical roles in cell survival. Cerebral ischemia is a major neural disorder with a high percentage of mortality and disability. Ischemia leads to energy depletion and eventually neuronal death and brain damage. This study investigated the role of PBEF in cerebral ischemia using a photothrombosis mouse model. Using immunostaining, we initially determined that PBEF is highly expressed in neurons, but not in glial cells in the mouse brain. To study the role of PBEF in ischemia in vivo, we used PBEF knockout heterozygous (Pbef+/−) mice. We showed that these mice have lower PBEF expression and NAD+ level than do wild-type (WT) mice. When subjected to photothrombosis, Pbef+/− mice have significantly larger infarct volume than do age-matched WT mice at 24 hours after ischemia. Higher density of degenerating neurons was detected in the penumbra of Pbef+/− mice than in WT mice using Fluoro-Jade B staining. Our study shows that PBEF has a neuronal protective role in cerebral ischemia presumably through enhanced energy metabolism.

scholarly journals Regulator of calcineurin 1 mediates pathological vascular wall remodeling

2011 ◽  
Vol 208 (10) ◽  
pp. 2125-2139 ◽  
Author(s):  
Vanesa Esteban ◽  
Nerea Méndez-Barbero ◽  
Luis Jesús Jiménez-Borreguero ◽  
Mercè Roqué ◽  
Laura Novensá ◽  
...  
Keyword(s):  
Aortic Wall ◽  
Vascular Wall ◽  
Potential Therapeutic Target ◽  
Whole Genome Analysis ◽  
Inhibitory Peptides ◽  
Aneurysm Formation ◽  
Vessel Remodeling ◽  
Vessel Lumen

Artery wall remodeling, a major feature of diseases such as hypertension, restenosis, atherosclerosis, and aneurysm, involves changes in the tunica media mass that reduce or increase the vessel lumen. The identification of molecules involved in vessel remodeling could aid the development of improved treatments for these pathologies. Angiotensin II (AngII) is a key effector of aortic wall remodeling that contributes to aneurysm formation and restenosis through incompletely defined signaling pathways. We show that AngII induces vascular smooth muscle cell (VSMC) migration and vessel remodeling in mouse models of restenosis and aneurysm. These effects were prevented by pharmacological inhibition of calcineurin (CN) or lentiviral delivery of CN-inhibitory peptides. Whole-genome analysis revealed &gt;1,500 AngII-regulated genes in VSMCs, with just 11 of them requiring CN activation. Of these, the most sensitive to CN activation was regulator of CN 1 (Rcan1). Rcan1 was strongly activated by AngII in vitro and in vivo and was required for AngII-induced VSMC migration. Remarkably, Rcan1−/− mice were resistant to AngII-induced aneurysm and restenosis. Our results indicate that aneurysm formation and restenosis share mechanistic elements and identify Rcan1 as a potential therapeutic target for prevention of aneurysm and restenosis progression.

scholarly journals Unique Human and Mouse β-cell Senescence-Associated Secretory Phenotype (SASP) Reveal Conserved Signaling Pathways and Heterogeneous Factors

2021 ◽  
Author(s):  
Ayush Midha ◽  
Hui Pan ◽  
Cristian Abarca ◽  
Joshua Andle ◽  
Priscila Carapeto ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Mouse Model ◽  
Cell Senescence ◽  
Cellular Stress Response ◽  
Matrix Remodeling ◽  
Β Cells ◽  
Β Cell ◽  
Potential Implication ◽  
Secretory Phenotype

The aging of pancreatic β-cells may undermine their ability to compensate for insulin resistance, leading to the development of type 2 diabetes (T2D). Aging β-cells acquire markers of cellular senescence and develop a senescence-associated secretory phenotype (SASP) that can lead to senescence and dysfunction of neighboring cells through paracrine actions, contributing to b-cell failure. Herein, we defined the β-cell SASP signature based on unbiased proteomic analysis of conditioned media of cells obtained from mouse and human senescent β-cells and a chemically-induced mouse model of DNA damage capable of inducing SASP. These experiments revealed that the β-cell SASP is enriched for factors associated with inflammation, cellular stress response, and extracellular matrix remodeling across species. Multiple SASP factors were transcriptionally upregulated in models of β-cell senescence, aging, insulin resistance and T2D. Single-cell transcriptomic analysis of islets from an <i>in vivo</i> mouse model of reversible insulin resistance indicated unique and partly reversible changes in β-cell subpopulations associated with senescence. Collectively, these results demonstrate the unique secretory profile of senescent b-cells and its potential implication in health and disease.

scholarly journals Angelica Sinensis Polysaccharide Prevents Hematopoietic Stem Cells Senescence in D-Galactose-Induced Aging Mouse Model

2017 ◽  
Vol 2017 ◽  
pp. 1-12 ◽  
Author(s):  
Xinyi Mu ◽  
Yanyan Zhang ◽  
Jing Li ◽  
Jieyu Xia ◽  
Xiongbin Chen ◽  
...  
Keyword(s):  
Mouse Model ◽  
Nuclear Translocation ◽  
Protective Role ◽  
Positive Control ◽  
Angelica Sinensis ◽  
Dna Double Strand Breaks ◽  
Hematopoietic Stem ◽  
Age Related ◽  
Aging Mouse

Age-related regression in hematopoietic stem/progenitor cells (HSC/HPCs) limits replenishment of the blood and immune system and hence contributes to hematopoietic diseases and declined immunity. In this study, we employed D-gal-induced aging mouse model and observed the antiaging effects of Angelica Sinensis Polysaccharide (ASP), a major active ingredient in dong quai (Chinese Angelica Sinensis), on the Sca-1+ HSC/HPCs in vivo. ASP treatment prevents HSC/HPCs senescence with decreased AGEs levels in the serum, reduced SA-β-Gal positive cells, and promoted CFU-Mix formation in the D-gal administrated mouse. We further found that multiple mechanisms were involved: (1) ASP treatment prevented oxidative damage as total antioxidant capacity was increased and levels of reactive oxygen species (ROS), 8-OHdG, and 4-HNE were declined, (2) ASP reduced the expression of γ-H2A.X which is a DNA double strand breaks (DSBs) marker and decreased the subsequent ectopic expressions of effectors in p16Ink4a-RB and p19Arf-p21Cip1/Waf senescent pathways, and (3) ASP inhibited the excessive activation of Wnt/β-catenin signaling in aged HSC/HPCs, as the expressions of β-catenin, phospho-GSK-3β, and TCF-4 were decreased, and the cyto-nuclear translocation of β-catenin was inhibited. Moreover, compared with the positive control of Vitamin E, ASP exhibited a better antiaging effect and a weaker antioxidation ability, suggesting a novel protective role of ASP in the hematopoietic system.

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