scholarly journals Circulating senescent angiogenic T cells are linked with endothelial dysfunction and systemic inflammation in hypertension

2020 ◽  
Vol Publish Ahead of Print ◽  
Author(s):  
Gaoxing Zhang ◽  
Yuanya Liu ◽  
Yumin Qiu ◽  
Jianning Zhang ◽  
Jiapan Sun ◽  
...  
Keyword(s):  
T Cells ◽  
Endothelial Dysfunction ◽  
Systemic Inflammation ◽  
Angiogenic T Cells

scholarly journals AB0026 DECREASE OF ANGIOGENIC T CELLS IN CONNECTIVE TISSUE DISEASE-ASSOCIATED INTERSTITIAL LUNG DISEASE

2021 ◽  
Vol 80 (Suppl 1) ◽  
pp. 1046.3-1047
Author(s):  
V. Pulito-Cueto ◽  
S. Remuzgo Martinez ◽  
F. Genre ◽  
B. Atienza-Mateo ◽  
V. M. Mora-Cuesta ◽  
...  
Keyword(s):  
T Cells ◽  
Interstitial Lung Disease ◽  
Connective Tissue ◽  
Lung Disease ◽  
Cell Subset ◽  
Vascular Damage ◽  
Type I ◽  
Research Support ◽  
Angiogenic T Cells

Background:Interstitial lung disease (ILD) is one of the most significant complications of connective tissue diseases (CTD), leading to an increase of the morbidity and mortality in patients with CTD [1]. A specific T cell subset termed angiogenic T cells (TAng), that promote endothelial repair and revascularization, have been involved in the pathogenesis of CTD [2-4]. However, to the best of our knowledge, no information regarding the role of TAng in CTD-ILD+ is available.Objectives:To study, for the first time, the potential role of TAng related to vascular damage in CTD-ILD+.Methods:Peripheral venous blood was collected from 40 patients with CTD-ILD+ and three comparative groups: 44 CTD-ILD- patients, 21 idiopathic pulmonary fibrosis (IPF) patients and 20 healthy controls (HC). All subjects were recruited from the Rheumatology and Pneumology departments of Hospital Universitario Marqués de Valdecilla, Santander, Spain. Quantification of TAng was performed by flow cytometry. TAng were considered as triple-positive for CD3, CD31 and CXCR4.Results:Patients with CTD-ILD+ exhibited a significantly lower TAng frequency than CTD-ILD- patients (p<0.001). Similar results were obtained when patients with CTD-ILD+ were compared with HC (p=0.004) although no difference was observed between CTD-ILD+ and IPF. In addition, a significant increase of TAng frequency was shown in patients with CTD-ILD- in relation to IPF patients (p<0.001), while no difference was observed between CTD-ILD- and HC.Conclusion:Our results reveal a decrease of TAng frequency related to vascular damage in CTD-ILD+. Furthermore, we disclose that the presence of ILD is associated with lower TAng frequency.References:[1]Expert Rev Clin Immunol 2018;14(1):69-82.[2]Circulation 2007;116(15):1671-82.[3]Ann Rheum Dis 2015 74(5):921-7.[4]PLoS One 2017;12(8):e0183102.Acknowledgements:Personal funds, VP-C: PREVAL18/01 (IDIVAL); SR-M: RD16/0012/0009 (ISCIII-ERDF); LL-G: INNVAL20/06 (IDIVAL); RP-F: START PROJECT (FOREUM); RL-M: Miguel Servet type I CP16/00033 (ISCIII-ESF).Disclosure of Interests:Verónica Pulito-Cueto: None declared, Sara Remuzgo Martinez: None declared, Fernanda Genre: None declared, Belén Atienza-Mateo: None declared, Victor Manuel Mora-Cuesta: None declared, David Iturbe-Fernández: None declared, Leticia Lera-Gómez: None declared, Raquel Pérez-Fernández: None declared, Pilar Alonso Lecue: None declared, Javier Rodriguez Carrio: None declared, Diana Prieto-Peña: None declared, Virginia Portilla: None declared, Ricardo Blanco Speakers bureau: Abbvie, Pfizer, Roche, Bristol-Myers, Janssen and MSD, Consultant of: Abbvie, Pfizer, Roche, Bristol-Myers, Janssen and MSD, Grant/research support from: Abbvie, MSD and Roche, Alfonso Corrales: None declared, Jose Manuel Cifrián-Martínez: None declared, Raquel López-Mejías: None declared, Miguel A González-Gay Speakers bureau: Pfizer, Abbvie, MSD, Grant/research support from: Pfizer, Abbvie, MSD

ENDOTHELIAL DYSFUNCTION AND SPECIFIC SYSTEMIC INFLAMMATION IN OBESITY HYPOVENTILATION SYNDROME

CHEST Journal ◽  
2009 ◽  
Vol 136 (4) ◽  
pp. 104S
Author(s):  
Jean-Christian Borel ◽  
Pascale Roux-Lombard ◽  
Renaud Tamisier ◽  
Claire Arnaud ◽  
Denis Monneret ◽  
...  
Keyword(s):  
Endothelial Dysfunction ◽  
Systemic Inflammation ◽  
Obesity Hypoventilation Syndrome ◽  
Hypoventilation Syndrome ◽  
Obesity Hypoventilation

scholarly journals Association of Helicobacter pyloriinfection with systemic inflammation and endothelial dysfunction in healthy male subjects

2005 ◽  
Vol 45 (8) ◽  
pp. 1219-1222 ◽  
Author(s):  
Tetsuya Oshima ◽  
Ryoji Ozono ◽  
Yoko Yano ◽  
Yoshihiko Oishi ◽  
Hiroki Teragawa ◽  
...  
Keyword(s):  
Endothelial Dysfunction ◽  
Systemic Inflammation ◽  
Healthy Male ◽  
Male Subjects

Preeclampsia Part 2: fisiopatologia e trattamento

2019 ◽  
Vol 31 (2) ◽  
pp. 79-88
Author(s):  
Stefano Michelassi
Keyword(s):  
High Risk ◽  
Endothelial Dysfunction ◽  
Preterm Delivery ◽  
Systemic Inflammation ◽  
Systemic Disease ◽  
Clinical Manifestations ◽  
Morbidity And Mortality ◽  
Curative Treatment ◽  
Maternal Risks ◽  
New Onset

Preeclampsia is a pregnancy-specific disorder usually defined as new-onset hypertension and proteinuria after the 20th week of gestation. Preeclampsia is a systemic disease with multiorgan involvement, and it is associated with a high risk of maternal and fetal morbidity and mortality. To date its pathogenesis is not completely understood, but placental hypoxia or hypoxia/reoxigenation may be the basic condition leading to systemic inflammation and endothelial dysfunction that induce all the clinical manifestations of the disorder. Delivery is the only curative treatment. Indeed, for the management of preeclampsia one needs to consider both the maternal risks due to continued pregnancy and the fetal risks associated with induced preterm delivery.

Abstract 095: CD74 Deficient Mice are Resistant to Toll-Like Receptor-Induced Preeclampsia

Hypertension ◽  
2014 ◽  
Vol 64 (suppl_1) ◽  
Author(s):  
Mohamad Hatahet ◽  
Olga Y Gasheva ◽  
Valorie L Chiasson ◽  
Piyali Chatterjee ◽  
Kelsey R Bounds ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Endothelial Dysfunction ◽  
Mhc Class Ii ◽  
Immune Cells ◽  
Immune Cell ◽  
Class Ii ◽  
Poly I:C ◽  
Hypertensive Disorder ◽  
Toll Like Receptor

Preeclampsia (PE) is a pregnancy-specific hypertensive disorder characterized by vascular endothelial dysfunction and excessive immunity and inflammation. Activation of the dsRNA receptor Toll-like receptor 3 (TLR3) or the ssRNA receptor TLR7 elicits a pregnancy-dependent PE-like syndrome in mice by inducing a pro-inflammatory immune response. CD74 (MHC Class II invariant chain) acts as a chaperone for MHC Class II surface expression on immune cells during antigen presentation and is cleaved into Class II-Associated Invariant Peptide (CLIP) following polyclonal activation of immune cell TLRs. The presence of CLIP in the groove of MHC Class II prevents T cell-dependent death leading to persistent immune cell activation. We hypothesized that genetic deletion of CD74 and subsequent depletion of CLIP on immune cells prevents TLR-induced immune responses and the development of PE in mice. Pregnant WT and CD74 KO mice were given i.p. injections of normal saline (P), poly I:C (TLR3 agonist; P-PIC), or R837 (TLR7 agonist; P-R837) on gestational days 13, 15, and 17 and euthanized on day 18. P-PIC and P-R837 WT mice had significantly increased splenic levels of pro-inflammatory CD3+/gd T cells and plasma levels of the gd T cell-derived cytokines IFNg, TNFa, and IL-17 compared to P WT mice whereas P-PIC and P-R837 CD74 KO mice had significantly increased anti-inflammatory CD3+/gd T cells and no significant increases in plasma IFNg, TNFa, and IL-17 levels. P-PIC and P-R837 CD74 KO mice did not develop the hypertension (gd17 SBP in mmHg: P WT=102±3, P CD74 KO=100±3, P-PIC WT=147±4*, P-PIC CD74 KO=95±3, P-R837 WT=133±2*, P-R837 CD74 KO=97±1; *p<0.05 vs. P WT), endothelial dysfunction, proteinuria, or placental necrosis seen in P-PIC and P-R837 WT mice. In conclusion, CD74 is crucial for the development of TLR-induced PE-like symptoms in mice and CD74/CLIP depletion may be a promising therapeutic target for women with PE.

Remote Ischemic Preconditioning Protects Against Endothelial Dysfunction in a Human Model of Systemic Inflammation: A Randomized Clinical Trial

2021 ◽  
Author(s):  
Marco Orlandi ◽  
Stefano Masi ◽  
Devina Bhowruth ◽  
Yago Leira ◽  
Georgios Georgiopoulos ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Endothelial Dysfunction ◽  
Systemic Inflammation ◽  
Ischemic Preconditioning ◽  
Ischemia Reperfusion ◽  
Remote Ischemic Preconditioning ◽  
Human Model ◽  
Control Group ◽  
Flow Mediated Dilatation ◽  
And Oxidative Stress

Objective: Inflammation, oxidative stress, and endothelial dysfunction are known to contribute to ischemia-reperfusion injury. Remote ischemic preconditioning (RIPC) protects from endothelial dysfunction and the damage induced by ischemia-reperfusion. Using intensive periodontal treatment (IPT), an established human model of acute systemic inflammation, we investigated whether RIPC prevents endothelial dysfunction and modulates systemic levels of inflammation and oxidative stress. Approach and Results: Forty-nine participants with periodontitis were randomly allocated to receive either 3 cycles of ischemia-reperfusion on the upper limb (N=25, RIPC) or a sham procedure (N=24, control) before IPT. Endothelial function assessed by flow-mediated dilatation of the brachial artery, inflammatory cytokines, markers of vascular injury, and oxidative stress were evaluated at baseline, day 1, and day 7 after IPT. Twenty-four hours post-IPT, the RIPC group had lower levels of IL (interleukin)-10 and IL-12 compared with the control group ( P <0.05). RIPC attenuated the IPT-induced increase in IL-1β, E-selectin, sICAM-3 (soluble intercellular adhesion molecule 3), and s-thrombomodulin levels between the baseline and day 1 ( P for interaction <0.1). Conversely, oxidative stress was differentially increased at day1 in the RIPC group compared with the control group ( P for interaction <0.1). This was accompanied by a better flow-mediated dilatation (mean difference 1.75% [95% CI, 0.428–3.07], P =0.011). After 7 days from IPT, most of the inflammatory markers endothelial-dependent and -independent vasodilation were similar between groups. Conclusions: RIPC prevented acute endothelial dysfunction by modulation of inflammation and oxidation processes in patients with periodontitis following exposure to an acute inflammatory stimulus. REGISTRATION: URL: https://www.clinicaltrials.gov ; Unique identifier: NCT03072342.

Abstract 14723: Autoreactive T Lymphocytes Activate Cardiac Endothelium Independently of Tnf-α and Cause Endothelial Dysfunction Through Exosomes in Experimental Autoimmune Myocarditis

Circulation ◽  
2020 ◽  
Vol 142 (Suppl_3) ◽  
Author(s):  
Filip Rolski ◽  
Marcin Czepiel ◽  
Kazimierz Weglarczyk ◽  
Maciej Siedlar ◽  
Gabriela Kania ◽  
...  
Keyword(s):  
T Cells ◽  
Endothelial Dysfunction ◽  
T Lymphocytes ◽  
Conditioned Medium ◽  
Autoimmune Myocarditis ◽  
Autoreactive T Cells ◽  
Tnf Α ◽  
Experimental Autoimmune Myocarditis ◽  
Experimental Autoimmune ◽  
Stimulation Of

Background: Inflammatory heart diseases represent an important clinical problem, nonetheless data regarding activation of cardiac microvascular endothelial cells (MVECs) are limited. Aim: To examine influence of TNF-α and exosomes produced by heart-reactive CD4+ T lymphocytes on activation of cardiac MVECs. Methods: Experimental autoimmune myocarditis (EAM) was induced in wild-type (WT) and TNF-α-deficient (TNF-KO) mice. CD4+ T lymphocytes were isolated from EAM mice at day 21 and activated in vitro to produce conditioned medium and exosomes. Activation of MVECs was assessed by specific assays and leukocyte-to-endothelial adhesion was analysed under shear flow condition using the BioFlux microfluidic system. Results: TNF-KO mice showed lower prevalence of myocarditis when compared to WT mice (50% vs. 90%). Stimulation of MVECs with secretome of antigen-activated autoreactive T cells resulted in upregulation of adhesion molecules (ICAM-1, VCAM-1 and P-selectin), increased ROS and decreased NO production. Addition of anti-TNF-α neutralizing antibodies effectively blocked adhesion of leukocytes to MVECs activated with the conditioned medium. Endothelial activation and dysfunction induced by the conditioned medium were independent of TNF-α produced by T cells. Stimulation of MVECs with T cell-derived exosomes increased ROS and decreased levels of NO and eNOS activation, but exosomes neither increased expression of adhesion molecules in MVECs nor induced their ability to bind leukocytes. Conclusions: TNF-α promotes MVEC activation and EAM development. In this model, autoreactive T cells activate MVECs, and TNF-a produced by MVECs rather than T cells is essential in this process. On the other hand, endothelial dysfunction caused by T cells seems to be mediated mainly by exosomes.

P4679Changes in systemic inflammation and endothelial dysfunction after balloon pulmonary angioplasty

2019 ◽  
Vol 40 (Supplement_1) ◽  
Author(s):  
W Magon ◽  
J Stepniewski ◽  
K Jonas ◽  
M Waligora ◽  
P Podolec ◽  
...  
Keyword(s):  
Endothelial Dysfunction ◽  
Serum Concentration ◽  
Systemic Inflammation ◽  
Interleukin 6 ◽  
C Reactive Protein ◽  
Pulmonary Hemodynamics ◽  
Endothelin 1 ◽  
Reactive Protein ◽  
Balloon Pulmonary Angioplasty

Abstract Introduction Pulmonary endarterectomy leads to a decrease in systemic inflammation and improvement in endothelial function in patients with chronic thromboembolic pulmonary hypertension (CTEPH). Balloon pulmonary angioplasty (BPA) improves pulmonary hemodynamics in patients with inoperable CTEPH. Aim To assess changes in systemic inflammation and endothelial dysfunction after a single BPA session and after completion of the treatment. Methods We enrolled consecutive, inoperable CTEPH patients who underwent BPA. Interleukin 6, 10 (IL-6, IL-10), and C-reactive protein (hsCRP) constituted markers of systemic inflammation. Endothelin-1 (ET-1) served as a marker of endothelial dysfunction. Serum concentration of selected markers was assessed in every patient before, 24 hours after the first BPA session and 6 months after completion of the BPA treatment. Age- and sex-matched healthy subjects served as a control group. Results We recruited 20 patients with inoperable CTEPH (6 males [30%]), aged 67 [61–74] years in New York Heart Association class III (n=19 [95%]) and II (n=1 [5%]). BPA treatment was completed with a median of 5 [2–8] BPA sessions per patient. Before starting the treatment CTEPH patients, as compared to controls (n=10), had raised serum level of IL-6 (3.82 [2.75 - 6.03] vs. 2.64 [0.88 - 4.75] pg/ml; p=0.04), hsCRP (2.47 [0.93 - 4.27] vs. 1.23 [0.48–3.21] ng/ml; p=0.02) and ET-1 (2.68 [2.24 - 3.64] vs. 1.47 [1.4 - 1.82] pg/ml; p=0.004). There was no difference in IL-10 level. 24 hours after a BPA session we observed an increased level of IL-6, IL-10 and hsCRP. (Tab.) 6 months after completion of the BPA treatment there was a reduced level of IL-6, hsCRP and ET-1 (Tab.) Table 1. Changes (Δ) in serum concentration of analyzed markers 24 hours after a single BPA session and at 6-months assessment after completion of the BPA treatment (n=20) Initial Δ at 24 hours after single BPA p Δ at 6-months follow-up p ET-1 [pg/ml] 2.68 [2.24; 3.64] −0.2 [−0.5; 0.23] 0.21 −0.47 [−0.96; 0.05] 0.004 IL-6 [pg/ml] 3.82 [2.75; 6.03] 3.67 [1.41; 7.16] 0.008 −0.82 [−3.11; 0.54] 0.04 IL-10 [pg/ml] 0.53 [0.44; 0.58] 0.32 [0.21; 0.87] 0.006 −0.11 [−0.33; 0.14] 0.94 hsCRP [ng/ml] 2.47 [0.93; 4.27] 5.4 [3.96; 10.59] 0.008 −0.36 [−0.94; 0.16] 0.02 ET-1, endothelin 1; hsCRP, C-reactive protein; IL-6, interleukin 6; IL-10, interleukin 10. Conclusions Patients with inoperable CTEPH, as compared to healthy controls, exhibit an increased systemic inflammation and endothelial dysfunction, which both improve after completion of the BPA treatment. At short-term follow-up after single BPA session there is an increase in systemic inflammatory response.

scholarly journals Immunoinflammatory Profile in Patients with Episodic and Continuous Paranoid Schizophrenia

10.17816/cp66 ◽  
2021 ◽  
Vol 2 (1) ◽  
pp. 19-31
Author(s):  
Irina K. Malashenkova ◽  
Sergey A. Krynskiy ◽  
Daniil P. Ogurtsov ◽  
Nikita A. Hailov ◽  
Natalia V. Zakharova ◽  
...  
Keyword(s):  
Immune Response ◽  
T Cells ◽  
Adaptive Immunity ◽  
Systemic Inflammation ◽  
Negative Symptoms ◽  
Clinical Course ◽  
Paranoid Schizophrenia ◽  
C Reactive Protein ◽  
Reactive Protein ◽  
Positive And Negative Symptoms

Introduction. Associations of disturbances in innate and adaptive immunity during the clinical course of schizophrenia have been found in a number of studies. Yet, the relationship of immune parameters and systemic inflammation in relation to the clinical course of the disease and its prognosis, remains poorly understood, which highlights an interesting topic for further research. The goal of this study was to research the immuno-inflammatory changes in patients with clinical continuous and episodic paranoid schizophrenia, to assess the pathogenetic significance of these changes. Methods. Thirty-six patients with paranoid schizophrenia, of which 20 had episodic symptoms and 16 had continuous symptoms, consented to participate in the study, together with 30 healthy volunteers. In the study we assessed the parameters of innate immune response (serum levels of key pro-inflammatory and anti-inflammatory cytokines, C-reactive protein) and the adaptive immune response, including humoral-mediated immunity (serum immunoglobulins IgA, IgM, IgG, circulating immune complexes), as well as the cell link of adaptive immunity (key lymphocyte subpopulations). Positive and negative symptoms were assessed with the positive and negative symptoms scale; frontal dysfunction was assessed by Frontal Assessment Battery (FAB). Results. Both patient groups had higher than normal levels of C-reactive protein and IL-8. There was a significant elevation of circulating immune complexes among patients with continuous symptoms of schizophrenia, compared to patients with episodic symptoms and healthy controls. Levels of CD45+CD3+ lymphocytes (T-cells) differed between clinical groups, with higher values identified among patients with episodic symptoms and lower values among those with continuous symptoms. In addition, patients with episodic symptoms had significantly increased levels of CD45+CD3+CD4+CD25+CD127- regulatory T-cells. Finally, the level of CD45+CD3-CD19+ B-cells was significantly higher among patients with continuous symptoms vs. patients with episodic symptoms and the control groups. Markers of activation of humoral immunity were associated with the severity of frontal disorders in these patients. Discussion. Comprehensive data on the serum level of cytokines and the parameters of adaptive immunity among individuals with continuous schizophrenia, by comparison with patients with episodic schizophrenia, are practically absent in the literature. We have shown that among those with continuous schizophrenia, there are signs of systemic inflammation and chronic activation of the adaptive humoral immune response, while among patients with episodic symptoms of the disease, there are signs of systemic inflammation and certain activation of cell-mediated immunity, without significant changes in the humoral link of adaptive immunity. Conclusion. More studies are needed, but the data obtained in this study are important for subsequent clinical studies of new treatment methods, based on various immunophenotypes of schizophrenia.

Abstract 66: The Role of the Viral Nef Protein as a Mediator of HIV-1--Induced Endothelial Dysfunction

2012 ◽  
Vol 111 (suppl_1) ◽  
Author(s):  
Ting Wang
Keyword(s):  
Cardiovascular Disease ◽  
T Cells ◽  
Endothelial Cells ◽  
Endothelial Cell ◽  
Endothelial Dysfunction ◽  
Binding Site ◽  
Cell Activation ◽  
Endothelial Activation ◽  
Endothelial Cell Activation ◽  
Hiv 1

With the prevalence of antiviral therapy in the developed world, many HIV-1-infected people die of diseases other than AIDS. One of the emerging major causes is cardiovascular disease, leading to the prediction that the majority of HIV-1 patients are expected to develop cardiovascular complications. Endothelial dysfunction is thought to be a key event in the development of cardiovascular diseases, particularly atherosclerosis. Assays testing the effect of HIV-1 on endothelial activation shows that direct contact with HIV-1 infected T cells enhance endothelial cell activation to a greater extent than HIV-1 alone, suggesting an intracellular HIV-1 protein is responsible for endothelial activation. The HIV-1 viral protein Nef, which is responsible for T cell activation and maintenance of high viral loads in vivo , has been shown to mediate its own transfer to bystander cells. We demonstrate here for the first time that Nef induces nanotube-like conduits connecting T cells and endothelial cells. We also show that Nef is transferred from T cells to endothelial cells via these nanotubes, and is necessary and sufficient for endothelial cell activation. Moreover, we show that SIV-infected macaques exhibit endothelial Nef expression in coronary arteries. Nef expression in endothelial cells causes endothelial apoptosis, ROS and MCP-1 production. Interestingly, a Nef SH3 binding site mutant abolishes Nef-induced apoptosis and ROS formation and reduces MCP-1 production in endothelial cells, suggesting that the Nef SH3 binding site is critical for Nef effects on endothelial cells. Nef induces apoptosis of endothelial cells through an NADPH oxidase- and ROS-dependent mechanism, while Nef-induced MCP-1 production is NF-kB dependent. Taken together, these data suggest that Nef can mediate its transfer from T cells to endothelial cells through nanotubes to enhance endothelial dysfunction.Thus, Nef is a promising new therapeutic target for reducing the risk for cardiovascular disease in the HIV-1 positive population.

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