scholarly journals GLP-1 Analog Liraglutide Improves Vascular Function in Polymicrobial Sepsis by Reduction of Oxidative Stress and Inflammation

Antioxidants ◽  
2021 ◽  
Vol 10 (8) ◽  
pp. 1175
Author(s):  
Johanna Helmstädter ◽  
Karin Keppeler ◽  
Franziska Aust ◽  
Leonie Küster ◽  
Katie Frenis ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Vascular Function ◽  
Vascular Inflammation ◽  
Cecal Ligation ◽  
Isometric Tension ◽  
Polymicrobial Sepsis ◽  
Dot Blot ◽  
Markers Of Inflammation ◽  
Anti Inflammatory ◽  
And Oxidative Stress

Sepsis causes high mortality in the setting of septic shock. LEADER and other trials revealed cardioprotective and anti-inflammatory properties of glucagon-like peptide-1 (GLP-1) analogs like liraglutide (Lira). We previously demonstrated improved survival in lipopolysaccharide (LPS)-induced endotoxemia by inhibition of GLP-1 degradation. Here we investigate the effects of Lira in the polymicrobial sepsis model of cecal ligation and puncture (CLP). C57BL/6J mice were intraperitoneally injected with Lira (200 µg/kg/d; 3 days) and sepsis induced by CLP after one day of GLP-1 analog treatment. Survival and body temperature were monitored. Aortic vascular function (isometric tension recording), protein expression (immunohistochemistry and dot blot) and gene expression (qRT-PCR) were determined. Endothelium-dependent relaxation in the aorta was impaired by CLP and correlated with markers of inflammation (e.g., interleukin 6 and inducible nitric oxide synthase) and oxidative stress (e.g., 3-nitrotyrosine) was higher in septic mice, all of which was almost completely normalized by Lira therapy. We demonstrate that the GLP-1 analog Lira ameliorates sepsis-induced endothelial dysfunction by the reduction of vascular inflammation and oxidative stress. Accordingly, the findings suggest that the antioxidant and anti-inflammatory effects of GLP-1 analogs may be a valuable tool to protect the cardiovascular system from dysbalanced inflammation in polymicrobial sepsis.

scholarly journals Garlic and Onion Attenuates Vascular Inflammation and Oxidative Stress in Fructose-Fed Rats

2011 ◽  
Vol 2011 ◽  
pp. 1-7 ◽  
Author(s):  
Marcela Alejandra Vazquez-Prieto ◽  
Cecilia Rodriguez Lanzi ◽  
Carina Lembo ◽  
Claudio Rómulo Galmarini ◽  
Roberto Miguel Miatello
Keyword(s):  
Oxidative Stress ◽  
Vascular Inflammation ◽  
Mesenteric Arteries ◽  
Male Wistar Rats ◽  
Anti Inflammatory ◽  
Oxide Synthase ◽  
Cell Adhesion Molecule 1 ◽  
Endothelial Nitric Oxide ◽  
New Evidence ◽  
And Oxidative Stress

This study evaluates the antioxidant and the anti-inflammatory properties of garlic (G) and onion (O) in fructose-fed rats (FFR). Thirty-day-old male Wistar rats were assigned to control (C), F (10% fructose in drinking water), F+T (tempol 1 mM as control antioxidant), F+G, and F+O. Aqueous G and O extracts were administered orally in doses of 150 and 400 mg/kg/d respectively, and along with tempol, were given during the last 8 weeks of a 14-week period. At the end of the study, FFR had developed insulin resistance, aortic NADPH oxidase activity, increased SBP, plasma TBARS and vascular cell adhesion molecule-1 (VCAM-1) expression in mesenteric arteries, and a decrease in heart endothelial nitric oxide synthase (eNOS). Garlic and onion administration to F rats reduced oxidative stress, increased eNOS activity, and also attenuated VCAM-1 expression. These results provide new evidence showing the anti-inflammatory and antioxidant effect of these vegetables.

scholarly journals POS1011 PREDICTORS OF ENDOTHELIAL DYSFUNCTION IN ANKYLOSING SPONDYLITIS

2021 ◽  
Vol 80 (Suppl 1) ◽  
pp. 774.1-774
Author(s):  
A. Syngle ◽  
N. Garg ◽  
I. Verma ◽  
P. Krishan
Keyword(s):  
Oxidative Stress ◽  
Ankylosing Spondylitis ◽  
Endothelial Dysfunction ◽  
Disease Activity ◽  
Vascular Function ◽  
Group Analysis ◽  
Predictive Biomarkers ◽  
Markers Of Inflammation ◽  
Tnf Α ◽  
And Oxidative Stress

Background:Cardiovascular (CV) disease is the leading cause of death in Ankylosing Spondylitis (AS). Chronic systemic inflammation driven endothelial dysfunction leading to accelerated atherosclerosis results in premature mortality. Endothelial dysfunction is potentially treatable hence a therapeutic target. Predictive biomarkers for endothelial dysfunction would allow tailoring therapy to the individual.Objectives:To assess the endothelial dysfunction in AS in context of markers of inflammation and oxidative stress in AS patients.Methods:Sub group–analysis of our previous studies of AS1-3 was carried out and 80 AS patients were compared with 40 healthy controls matched for age and sex that were also part of these studies.2,3 Such analysis had so far not been performed in this cohort. Patients with traditional CV risk factors had been excluded in these studies. Flow-mediated dilatation (FMD), as a measure of endothelial function, was assessed by AngioDefender (Everist Health, Ann Arbor, MI). Inflammatory measures included: Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) and Ankylosing Spondylitis Disease Activity Score (ASDAS) in AS. We also assayed markers of inflammation, including C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), proinflammatory cytokines (interleukin [IL]-1, IL-6, and tumor necrosis factor [TNF]-α), and endothelial dysfunction, including lipids and nitrite and marker of oxidative stress, TBARS.Results:FMD was significantly lower in AS patients compared with controls [(5.80±0.35% vs. 9.09±0.35%, p≤0.05) reduced by approximately 36%] whereas serum nitrite, TBARS, total cholesterol and LDL levels were significantly higher in AS compared with controls (p≤0.05). Compared with controls, AS patients had significantly high BASDAI, ASDAS and increased concentrations of ESR, CRP, TNF-α, and IL-6. In AS, FMD inversely correlated with ASDAS, CRP (Figure 1A), TNF-α (Figure 1B), nitrite (Figure 1C) and TBARS (Figure 1) and positively correlated with HDL (p≤0.05).Figure 1.Correlation of FMD with CRP, TNF-α, Nitrite and TBARSConclusion:In AS, FMD was impaired, indicating endothelial dysfunction. ASDAS, CRP, TNF-α, nitrite, and TBARS were independent predictors of FMD in AS. AS-related inflammatory mechanisms (TNF-α, IL-6) and markers of vascular function and oxidative stress (CRP, nitrite and TBARS) may all be involved in the development of cardiovascular disease in AS and these predictors could serve as a novel therapeutic targets for preventing CV risk in AS.References:[1]Garg N, Krishan P, Syngle A. Rosuvastatin improves endothelial dysfunction in ankylosing spondylitis. Clin Rheumatol. 2015;34:1065-1071.[2]Verma I, Syngle A, Krishan P, Garg N. Endothelial Progenitor Cells as a Marker of Endothelial Dysfunction and Atherosclerosis in Ankylosing Spondylitis. International Journal of Angiology. 2017;26:36–42.[3]Verma I, Krishan P, Syngle A. Predictors of Atherosclerosis in Ankylosing Spondylitis. Rheumatol Ther. 2015;2(2): 173–182.Disclosure of Interests:None declared.

P717Glucagon-like peptide 1 (GLP-1) improves endothelial dysfunction and vascular inflammation in polymicrobial sepsis induced by cecal ligation and puncture (CLP)

2019 ◽  
Vol 40 (Supplement_1) ◽  
Author(s):  
S Steven ◽  
J Helmstaedter ◽  
F Pawelke ◽  
K Filippou ◽  
K Frenies ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Clinical Trials ◽  
Endothelial Dysfunction ◽  
Knockout Mice ◽  
Vascular Inflammation ◽  
Cecal Ligation ◽  
Cecal Ligation And Puncture ◽  
Glucose Levels ◽  
Dpp4 Inhibitor ◽  
Cardioprotective Effects

Abstract Objective Sepsis causes severe hypotension, accompanied by high mortality in the setting of septic shock. LEADER, SUSTAIN-6 and other clinical trials revealed cardioprotective and anti-inflammatory properties of GLP-1 analogs like Liraglutide (Lira). We already demonstrated improved survival by amelioration of disseminated intravasal coagulation (DIC) in lipopolysaccharide (LPS)-induced endotoxemia by inhibition of the GLP-1 degrading enzyme dipeptidylpeptidase-4 (DPP-4). With the present study we aim to investigate the mechanism of protective effects of the GLP-1 analog Lira and the DPP4 inhibitor Linagliptin (Lina) in the clinically relevant sepsis model cecal ligation and puncture (CLP). Methods C57/BL6j and endothelial cell-specific GLP-1 receptor knockout mice (Cdh5crexGLP-1rfl/flmice) were used and sepsis was induced by cecal ligation and puncture (CLP). DPP4 inhibitor (Lina, 5mg/kg/d; 3 days) and GLP-1 analog (Lira, 200μg/kg/d; 3 days) were applied subcutaneously. Aortic vascular function was tested by isometric tension recording. Aorta and heart tissue was used for Western blotting, dot blot and qRT-PCR. Endogenous GLP-1 (7–36 and 9–36) and insulin was determined by ELISA. Blood samples were collected for examination of cell count, oxidative stress and glucose levels. Results Body temperature was increased by CLP and normalized by Lina and Lira. Sham- and Lira- but not Lina-treated septic mice showed low blood glucose levels compared to healthy controls. Acetylcholine-induced (endothelium-dependent) vascular relaxation in aorta was impaired by CLP. This was accompanied by vascular inflammation and elevation of IL-6, iNOS, ICAM-1, and TNF-alpha mRNA levels in aortic tissue. Vascular, cardiac and whole blood oxidative stress were increased by CLP. Furthermore, we detected higher levels of IL-6, 3-nitrotyrosine (3-NT) and 4-hydroxynonenal (4-NHE) in plasma of CLP animals. Lina and Lira reduced oxidative stress and vascular inflammation, which was accompanied by improved endothelial function. In addition, CLP treatment in endothelial specific knockout mice of the GLP-1r strongly induced mortality compared to WT mice, with the effect being strongest in the Lira-treated group. Conclusion The present study demonstrates that Lina (DPP4 inhibitor) and the GLP-1 analog Lira ameliorate sepsis-induced endothelial dysfunction by reduction of vascular inflammation and oxidative stress. Clinical trials like LEADER and SUSTAIN-6 proved that GLP-1 analogs like Lira have cardioprotective effects in T2DM patients. The present study, performed in a clinically relevant model of polymicrobial sepsis, reveals that the known cardioprotective effects of GLP-1 might be translated to other diseases which affect the cardiovascular system like sepsis, underlining the potent anti-inflammatory effects of GLP-1 analogs.

scholarly journals Coptisine Attenuates Diabetes—Associated Endothelial Dysfunction through Inhibition of Endoplasmic Reticulum Stress and Oxidative Stress

Molecules ◽  
2021 ◽  
Vol 26 (14) ◽  
pp. 4210
Author(s):  
Yan Zhou ◽  
Chunxiu Zhou ◽  
Xutao Zhang ◽  
Chi Teng Vong ◽  
Yitao Wang ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Risk Factors ◽  
Endoplasmic Reticulum ◽  
Er Stress ◽  
Vascular Function ◽  
Inflammatory Responses ◽  
Therapeutic Potential ◽  
Ex Vivo ◽  
Diabetic Mice ◽  
And Oxidative Stress

Coptisine is the major bioactive protoberberine alkaloid found in Rhizoma Coptidis. Coptisine reduces inflammatory responses and improves glucose tolerance; nevertheless, whether coptisine has vasoprotective effect in diabetes is not fully characterized. Conduit arteries including aortas and carotid arteries were obtained from male C57BL/6J mice for ex vivo treatment with risk factors (high glucose or tunicamycin) and coptisine. Some arterial rings were obtained from diabetic mice, which were induced by high-fat diet (45% kcal% fat) feeding for 6 weeks combined with a low-dose intraperitoneal injection of streptozotocin (120 mg/kg). Functional studies showed that coptisine protected endothelium-dependent relaxation in aortas against risk factors and from diabetic mice. Coptisine increased phosphorylations of AMPK and eNOS and downregulated the endoplasmic reticulum (ER) stress markers as determined by Western blotting. Coptisine elevates NO bioavailability and decreases reactive oxygen species level. The results indicate that coptisine improves vascular function in diabetes through suppression of ER stress and oxidative stress, implying the therapeutic potential of coptisine to treat diabetic vasculopathy.

scholarly journals Bone Marrow Mesenchymal Stromal Cells on Silk Fibroin Scaffolds to Attenuate Polymicrobial Sepsis Induced by Cecal Ligation and Puncture

Polymers ◽  
2021 ◽  
Vol 13 (9) ◽  
pp. 1433
Author(s):  
Ok-Hyeon Kim ◽  
Jun-Hyung Park ◽  
Jong-In Son ◽  
Ok-Ja Yoon ◽  
Hyun-Jung Lee
Keyword(s):  
Bone Marrow ◽  
Cecal Ligation ◽  
Biological Properties ◽  
Pge2 Production ◽  
Polymicrobial Sepsis ◽  
Control Surface ◽  
Related Factors ◽  
Cox 2 ◽  
Anti Inflammatory

Suitable scaffolds with appropriate mechanical and biological properties can improve mesenchymal stromal cell (MSC) therapy. Because silk fibroins (SFs) are biocompatible materials, they were electrospun and applied as scaffolds for MSC therapy. Consequently, interferon (IFN)-primed human bone marrow MSCs on SF nanofibers were administered into a polymicrobial sepsis murine model. The IL-6 level gradually decreased from 40 ng/mL at 6 h after sepsis to 35 ng/mL at 24 h after sepsis. The IL-6 level was significantly low as 5 ng/mL in primed MSCs on SF nanofibers, and 15 ng/mL in primed MSCs on the control surface. In contrast to the acute response, inflammation-related factors, including HO-1 and COX-2 in chronic liver tissue, were effectively inhibited by MSCs on both SF nanofibers and the control surface at the 5-day mark after sepsis. An in vitro study indicated that the anti-inflammatory function of MSCs on SF nanofibers was mediated through enhanced COX-2-PGE2 production, as indomethacin completely abrogated PGE2 production and decreased the survival rate of septic mice. Thus, SF nanofiber scaffolds potentiated the anti-inflammatory and immunomodulatory functions of MSCs, and were beneficial as a culture platform for the cell therapy of inflammatory disorders.

scholarly journals CD40L controls obesity-associated vascular inflammation, oxidative stress, and endothelial dysfunction in high fat diet-treated and db/db mice

2017 ◽  
Vol 114 (2) ◽  
pp. 312-323 ◽  
Author(s):  
Sebastian Steven ◽  
Mobin Dib ◽  
Michael Hausding ◽  
Fatemeh Kashani ◽  
Matthias Oelze ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Endothelial Dysfunction ◽  
High Fat Diet ◽  
Immune Cell ◽  
Vascular Inflammation ◽  
Human Study ◽  
Isometric Tension ◽  
Wild Type ◽  
High Fat ◽  
Aorta Ascendens

Abstract Aims CD40 ligand (CD40L) signaling controls vascular oxidative stress and related dysfunction in angiotensin-II-induced arterial hypertension by regulating vascular immune cell recruitment and platelet activation. Here we investigated the role of CD40L in experimental hyperlipidemia. Methods and results Male wild type and CD40L−/− mice (C57BL/6 background) were subjected to high fat diet for sixteen weeks. Weight, cholesterol, HDL, and LDL levels, endothelial function (isometric tension recording), oxidative stress (NADPH oxidase expression, dihydroethidium fluorescence) and inflammatory parameters (inducible nitric oxide synthase, interleukin-6 expression) were assessed. CD40L expression, weight, leptin and lipids were increased, and endothelial dysfunction, oxidative stress and inflammation were more pronounced in wild type mice on a high fat diet, all of which was almost normalized by CD40L deficiency. Similar results were obtained in diabetic db/db mice with CD40/TRAF6 inhibitor (6877002) therapy. In a small human study higher serum sCD40L levels and an inflammatory phenotype were detected in the blood and Aorta ascendens of obese patients (body mass index > 35) that underwent by-pass surgery. Conclusion CD40L controls obesity-associated vascular inflammation, oxidative stress and endothelial dysfunction in mice and potentially humans. Thus, CD40L represents a therapeutic target in lipid metabolic disorders which is a leading cause in cardiovascular disease.

scholarly journals Riboflavin Supplementation in Patients with Crohn’s Disease [the RISE-UP study]

2019 ◽  
Vol 14 (5) ◽  
pp. 595-607 ◽  
Author(s):  
Julius Z H von Martels ◽  
Arno R Bourgonje ◽  
Marjolein A Y Klaassen ◽  
Hassan A A Alkhalifah ◽  
Mehdi Sadaghian Sadabad ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Crohn’S Disease ◽  
Crohn's Disease ◽  
Disease Activity ◽  
Clinical Symptoms ◽  
Fish Analysis ◽  
Markers Of Inflammation ◽  
Anti Inflammatory ◽  
Faecal Microbiome ◽  
Chronic Intestinal Inflammation

Abstract Background and Aims Crohn’s disease [CD] is characterised by chronic intestinal inflammation and dysbiosis in the gut. Riboflavin [vitamin B2] has anti-inflammatory, antioxidant and microbiome-modulatory properties. Here, we analysed the effect of riboflavin on oxidative stress, markers of inflammation, clinical symptoms, and faecal microbiome in patients with CD. Methods In this prospective clinical intervention study, patients received 100 mg riboflavin [DSM, Nutritional Products Ltd] daily for 3 weeks. Clinical disease activity [Harvey-Bradshaw Index: HBI], serum biomarkers of inflammation and redox status [plasma free thiols], and faecal microbiome taxonomical composition and functionality [fluorescent in situ hybridisation: FISH; and metagenomic shotgun sequencing: MGS], were analysed before and after riboflavin intervention. Results In total, 70 patients with CD with varying disease activity were included. Riboflavin supplementation significantly decreased serum levels of inflammatory markers. In patients with low faecal calprotectin [FC] levels, IL-2 decreased, and in patients with high FC levels, C-reactive protein [CRP] was reduced and free thiols significantly increased after supplementation. Moreover, HBI was significantly decreased by riboflavin supplementation. Riboflavin supplementation led to decreased Enterobacteriaceae in patients with low FC levels as determined by FISH; however, MGS analysis showed no effects on diversity, taxonomy, or metabolic pathways of the faecal microbiome. Conclusions Three weeks of riboflavin supplementation resulted in a reduction in systemic oxidative stress, mixed anti-inflammatory effects, and a reduction in clinical symptoms [HBI]. FISH analysis showed decreased Enterobacteriaceae in patients with CD with low FC levels, though this was not observed in MGS analysis. Our data demonstrate that riboflavin supplementation has a number of anti-inflammatory and anti-oxidant effects in CD.

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