scholarly journals Correspondence on ‘A. Grylls, K. Seidler, J. Neil, Link between microbiota and hypertension: Focus on LPS/TLR4 pathway in endothelial dysfunction and vascular inflammation, and therapeutic implication of probiotics’

2021 ◽  
Vol 138 ◽  
pp. 111432
Author(s):  
Marco Tullio Suadoni
Keyword(s):  
Endothelial Dysfunction ◽  
Vascular Inflammation ◽  
Therapeutic Implication

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 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.

Abstract 368: Family History of Premature Cardiac Events and Sub Clinical Atherosclerosis in Children and Young Adults: A Systematic Review

2013 ◽  
Vol 33 (suppl_1) ◽  
Author(s):  
Pragya Sinha ◽  
Jamal S Rana ◽  
Ebenezer T Oni ◽  
Ehimen C Aneni ◽  
Roger S Blumenthal ◽  
...  
Keyword(s):  
Cardiovascular Disease ◽  
Young Adults ◽  
Family History ◽  
Endothelial Dysfunction ◽  
Subclinical Atherosclerosis ◽  
Vascular Inflammation ◽  
Positive Family History ◽  
Cardiac Risk Factor ◽  
Children And Young Adults ◽  
The Impact

BACKGROUND The association between a positive family history (PFH) of premature cardiovascular disease (PCVD) and atherosclerosis has been explored in numerous studies. In adults, various studies have confirmed a significant positive correlation between a PFH and PCVD. Scant literature however, focuses on young individuals. Nevertheless, it is important to understand the impact that a PFH has in young people because the foundations of atherosclerosis and adverse cardiac behaviors develop in youth. In this paper, we aimed to systematically review the evidence linking a PFH of PCVD to indirect markers of subclinical atherosclerosis. METHODS The search was conducted on Medline, Web of Science and Embase. ‘Family history’, ‘children/young adults’ and ‘subclinical atherosclerosis’ were the three main concepts used. Increase in mean carotid IMT (cIMT), endothelial dysfunction and vascular inflammation were used as indirect measures of subclinical atherosclerosis. RESULTS 1191 articles were identified in the initial search. 24 papers with 5400 participants were included in the final review. There were five cohort studies and nineteen case control studies from twelve countries. Mean cIMT was found to be significantly increased in those with a PFH by eleven of the fourteen papers reviewed. Endothelial dysfunction, measured by flow mediated dilatation (FMD), was found to be significantly increased in five of the seven included studies. The evidence on vascular inflammation was somewhat inconsistent with only ten of the nineteen studies demonstrating significance. The results tend to suggest that an elevated mean cIMT, as well as a greater degree of endothelial dysfunction are seen in children and young adults with a PFH of PCVD. Moreover, these differences exist in asymptomatic children as young as 8-9 years (4 studies) in the absence of any other cardiac risk factor. DISCUSSION Individuals with a PFH of PCVD have evidence of subclinical atherosclerosis in their youth demonstrating an accelerated tendency to acquire cardiovascular disease. Some of this risk may be attributable to behavioral risk clustering in families. However, a significant proportion of this elevated risk is related solely to a positive family history and needs attention.

Abstract MP07: Nicotine Promotes Vascular Inflammation And Endothelial Dysfunction In Obese Rats

Hypertension ◽  
2014 ◽  
Vol 64 (suppl_1) ◽  
Author(s):  
Ming-Sheng Zhou ◽  
Chang Liu ◽  
Kiranmai Chadipiralla ◽  
Runxia Tian ◽  
Leopoldo Raij
Keyword(s):  
Endothelial Dysfunction ◽  
Body Weight Gain ◽  
Synergistic Effects ◽  
Vascular Inflammation ◽  
Epidemiological Studies ◽  
Peritoneal Macrophages ◽  
Sprague Dawley ◽  
Diet Induced Obesity ◽  
Sd Rats ◽  
Receptor Signaling Pathway

Epidemiological studies have shown that obesity and cigarette smoking (CS) are major cardiovascular (CV) risk factors and when coexisting in the same individuals have additive/synergistic effects upon CVD development. We have shown that stable compounds of CS (ATVB 2004) as well as nicotine, in concentrations found in smoker’s plasma, promote atherosclerotic CVD (AJP 2013). Here we studied in Sprague Dawley (SD) rats with diet -induced obesity the mechanisms involved in nicotine enhancement of CVD. SD rats (N=6-7 each group) were fed either a high fat (HF) or a standard chow (SCH) diet with or without nicotine (100 mg/kg/day in the drinking water) for 20 weeks. The HF rats developed central obesity, characterized by increased body weight gain (22%) and abdominal fat weight (53%), increased plasma levels of cholesterol (33%), non-esterified free fatty acids (68%), insulin (15%) glucose (12%)and systolic blood pressure (SBP: 146 ± 5 vs. 131 ± 5 mmHg SCH rats, p<0.05). Nicotine further increased SBP in obese HF rats (158 ± 4 mmHg, p<0.05) but not in lean SCH rats. Nicotine significantly increased O2- production in both obese (1689 ± 87 count/min/mg) and lean rats (1074 ± 105 count/min/mg) and further impaired EDR (Emax: 74 ± 5%) in obese HF rats. Nicotine also increased the expression of the macrophage marker ED1 in the aortas of obese HF rats. In peritoneal macrophages from obese HF rats TNFα, IL1β and CD36 were increased, and were further significantly increased in nicotine-treated obese HF rats. Using PCR array for inflammatory cytokines and receptor signaling pathway we found that the aortas from obese HF rats showed 2-4 fold increases in expression of several chemokines and interleukin genes expression; nicotine further increased the expression of 11 pro-inflammatory genes in the aortas from obese HF rats. Our results suggest that nicotine dramatically aggravates the CV effects of diet -induced obesity by increasing oxidative stress, vascular inflammation and endothelial dysfunction. Clinically chronic inhalation of nicotine, as that delivered by E-cigarettes, by individuals unable to quit the habit may have an important pro-atherogenic effect, particularly in obese subjects.

Abstract 12375: Vascular Inflammation Evaluated by 18F-Fluorodeoxyglucose-Positron Emission Tomography/Computed Tomography is Associated With Endothelial Dysfunction

Circulation ◽  
2014 ◽  
Vol 130 (suppl_2) ◽  
Author(s):  
Akihiro Honda ◽  
Nobuhiro Tahara ◽  
Atsuko Tahara ◽  
Sachiyo Igata ◽  
Yoshikazu Nitta ◽  
...  
Keyword(s):  
Cardiovascular Disease ◽  
Positron Emission Tomography ◽  
Endothelial Dysfunction ◽  
Pet Imaging ◽  
Carotid Arteries ◽  
Vascular Inflammation ◽  
Emission Tomography ◽  
Percent Change ◽  
Positron Emission ◽  
Fat Volume

Background: Endothelial dysfunction is an initial step for atherosclerotic cardiovascular disease. However, involvement of vascular inflammation in endothelial dysfunction is not fully investigated in humans. We assessed the relationship between endothelial function and vascular inflammation evaluated by 18F-fluorodeoxyglucose (FDG)-positron emission tomography (PET) imaging. Methods and Results: We examined endothelial function and vascular inflammation, which were evaluated by flow-mediated dilation (FMD) of the brachial artery functionally and FDG-PET imaging of carotid arteries, respectively, in 128 subjects (83 males and 45 females; mean age 61.8 ± 10.0 years) who underwent a risk-screening test for cardiovascular disease in Kurume University Hospital. Vascular inflammation of the carotid arteries was measured by blood-normalized standardized uptake value, known as a target-to-background ratio (TBR). Mean percent change in vasodilation (percent change over the baseline values; %FMD) and carotid TBR were 5.60 ± 2.24 % and 1.43 ± 0.22, respectively. %FMD was less in men than in women. In univariate analysis, %FMD was inversely correlated with age (p=0.011), systolic blood pressure (p=0.014), carotid artery maximum intima-media thickness (p=0.014), HbA1c (p=0.020), visceral fat volume (p=0.005), or TBR values (p<0.001). Multiple stepwise regression analysis revealed that age (p=0.034), visceral fat volume (p=0.002), and TBR values (p<0.001) were independently associated with decreased %FMD (R2=0.245). Conclusions: We found here that vascular inflammation in the carotid arteries evaluated by FDG-PET was one of the independent association of decreased %FMD, thus suggesting that vascular inflammation might contribute to endothelial dysfunction in humans.

Sign in / Sign up

Export Citation Format

Share Document