2011

DOI: 10.1161/atvbaha.111.231431

|View full text |Cite

|

Sign up to set email alerts

|

Interleukin-33 Induces Expression of Adhesion Molecules and Inflammatory Activation in Human Endothelial Cells and in Human Atherosclerotic Plaques

Svitlana Demyanets

¹

,

Viktória Kónya

²

,

Stefan P. Kastl

³

et al.

Abstract: Objective-Interleukin (IL)-33 is the most recently described member of the IL-1 family of cytokines and it is a ligand of the ST2 receptor. While the effects of IL-33 on the immune system have been extensively studied, the properties of this cytokine in the cardiovascular system are much less investigated.

Help me understand this report

Search citation statements

Order By: Relevance

Paper Sections

Select...

Discussion2

Regulated Shear Stress Assays1

Citation Types

Supporting

16

Mentioning

169

Contrasting

0

Unclassified

2

Year Published

2012

2012

2017

2017

Publication Types

Select...

Article8

Book2

Relationship

Self Cite0

Independent10

Authors

Journals

Cited by 142 publications

(187 citation statements)

References 67 publications

Supporting

16

Mentioning

169

Contrasting

0

Unclassified

2

Order By: Relevance

“…It was hypothesized that IL-33/ST2 signaling may have protective effects during atherosclerosis by inducing a Th1-to-Th2 switch of immune responses (28 ). Furthermore, IL-33 and ST2 mRNA and protein expression were found in human atherosclerotic plaque (33 ). Very recently, differential expression of components of the IL-33/ST2 signaling was reported in adult human cardiac cells and cells of the cardiac vasculature (34 ).…”

Section: Discussionmentioning

confidence: 99%

Increased Soluble ST2 Predicts Long-term Mortality in Patients with Stable Coronary Artery Disease: Results from the Ludwigshafen Risk and Cardiovascular Health Study

¹

,

²

,

³

et al. 2014

Clinical Chemistry

View full text Add to dashboard Cite

BACKGROUND Soluble suppression of tumorigenicity 2 (sST2) has emerged as a strong prognostic biomarker in patients with heart failure and myocardial infarction. The aim of this study was to evaluate the long-term prognostic value of sST2 in patients with stable coronary artery disease (CAD). METHODS sST2 plasma concentrations were measured in 1345 patients with stable CAD referred for coronary angiography at a single tertiary care center. The primary endpoint was all-cause mortality. RESULTS During a median follow-up time of 9.8 years, 477 (36%) patients died. The median sST2 plasma concentration at baseline was significantly higher among decedents than survivors (21.4 vs 18.5 ng/mL; P < 0.001). In multivariate Cox proportional hazards regression analysis, sST2 was an independent predictor of all-cause mortality (risk ratio 1.16 per 1-SD increase in log-transformed values; 95% CI 1.05–1.29; P = 0.004). In the same multivariate analysis, amino-terminal pro–B-type natriuretic peptide (NT-proBNP) and high-sensitivity cardiac troponin T (hs-cTnT) were also independent predictors, whereas galectin-3 was not. Patients with sST2 in the highest quartile (>24.6 ng/mL) displayed a 2-fold increased risk of death in univariate analysis, which was attenuated but remained significant in a fully adjusted model (risk ratio 1.39; 95% CI 1.10–1.76; P = 0.006). Further analysis showed that the prognostic impact of sST2 was additive to NT-proBNP and hs-cTnT. Using a multibiomarker approach combining these 3 complementary makers, we demonstrated that patients with all 3 biomarkers in the highest quartiles had the poorest outcome. CONCLUSIONS In this cohort of patients with stable CAD, increased sST2 was an independent predictor of long-term all-cause mortality and provided complementary prognostic information to hs-cTnT and NT-proBNP.

“…It was hypothesized that IL-33/ST2 signaling may have protective effects during atherosclerosis by inducing a Th1-to-Th2 switch of immune responses (28 ). Furthermore, IL-33 and ST2 mRNA and protein expression were found in human atherosclerotic plaque (33 ). Very recently, differential expression of components of the IL-33/ST2 signaling was reported in adult human cardiac cells and cells of the cardiac vasculature (34 ).…”

Section: Discussionmentioning

confidence: 99%

Increased Soluble ST2 Predicts Long-term Mortality in Patients with Stable Coronary Artery Disease: Results from the Ludwigshafen Risk and Cardiovascular Health Study

¹

,

²

,

³

et al. 2014

Clinical Chemistry

View full text Add to dashboard Cite

BACKGROUND Soluble suppression of tumorigenicity 2 (sST2) has emerged as a strong prognostic biomarker in patients with heart failure and myocardial infarction. The aim of this study was to evaluate the long-term prognostic value of sST2 in patients with stable coronary artery disease (CAD). METHODS sST2 plasma concentrations were measured in 1345 patients with stable CAD referred for coronary angiography at a single tertiary care center. The primary endpoint was all-cause mortality. RESULTS During a median follow-up time of 9.8 years, 477 (36%) patients died. The median sST2 plasma concentration at baseline was significantly higher among decedents than survivors (21.4 vs 18.5 ng/mL; P < 0.001). In multivariate Cox proportional hazards regression analysis, sST2 was an independent predictor of all-cause mortality (risk ratio 1.16 per 1-SD increase in log-transformed values; 95% CI 1.05–1.29; P = 0.004). In the same multivariate analysis, amino-terminal pro–B-type natriuretic peptide (NT-proBNP) and high-sensitivity cardiac troponin T (hs-cTnT) were also independent predictors, whereas galectin-3 was not. Patients with sST2 in the highest quartile (>24.6 ng/mL) displayed a 2-fold increased risk of death in univariate analysis, which was attenuated but remained significant in a fully adjusted model (risk ratio 1.39; 95% CI 1.10–1.76; P = 0.006). Further analysis showed that the prognostic impact of sST2 was additive to NT-proBNP and hs-cTnT. Using a multibiomarker approach combining these 3 complementary makers, we demonstrated that patients with all 3 biomarkers in the highest quartiles had the poorest outcome. CONCLUSIONS In this cohort of patients with stable CAD, increased sST2 was an independent predictor of long-term all-cause mortality and provided complementary prognostic information to hs-cTnT and NT-proBNP.

“…Th1-and Th2-mediated diseases (16,48,49) as well as activation of ECs (18,50). Clinical data show altered IL-33 serum levels in rheumatoid arthritis, ulcerative colitis, or allergic rhinitis (reviewed in Ref.…”

Section: Discussionmentioning

confidence: 99%

Macrophage-Derived IL-33 Is a Critical Factor for Placental Growth

¹

,

²

,

³

et al. 2013

The Journal of Immunology

View full text Add to dashboard Cite

IL-33, the most recently discovered member of the IL-1 superfamily and ligand for the transmembrane form of ST2 (ST2L), has been linked to several human pathologies including rheumatoid arthritis, asthma, and cardiovascular disease. Deregulated levels of soluble ST2, the natural IL-33 inhibitor, have been reported in sera of preeclamptic patients. However, the role of IL-33 during healthy pregnancy remains elusive. In the current study, IL-33 was detected in the culture supernatants of human placental and decidual macrophages, identifying them as a major source of secreted IL-33 in the uteroplacental unit. Because flow cytometry and immunofluorescence stainings revealed membranous ST2L expression on specific trophoblast populations, we hypothesized that IL-33 stimulates trophoblasts in a paracrine manner. Indeed, BrdU incorporation assays revealed that recombinant human IL-33 significantly increased proliferation of primary trophoblasts as well as of villous cytotrophoblasts and cell column trophoblasts in placental explant cultures. These effects were fully abolished upon addition of soluble ST2. Interestingly, Western blot and immunofluorescence analyses demonstrated that IL-33 activates AKT and ERK1/2 in primary trophoblasts and placental explants. Inhibitors against PI3K (LY294002) and MEK1/2 (UO126) efficiently blocked IL-33–induced proliferation in all model systems used. In summary, with IL-33, we define for the first time, to our knowledge, a macrophage-derived regulator of placental growth during early pregnancy.

“…In contrast, sST2 appears to act as a decoy receptor for IL-33, blocking myocardial and vascular benefits (10)(11)(12). IL-33 is also expressed in endothelial cells (ECs) (13)(14)(15)(16), in which it induces angiogenesis (17), expression of adhesion molecules, and inflammatory activation (18). Here we report the surprising finding that endothelial IL-33 from pressure overload induces a selective systemic response, potentially linking hypertension with circulating factors that can affect the vasculature and other organs.…”

mentioning

confidence: 89%

Myocardial pressure overload induces systemic inflammation through endothelial cell IL-33

¹

,

²

,

³

et al. 2015

Proc. Natl. Acad. Sci. U.S.A.

View full text Add to dashboard Cite

Hypertension increases the pressure load on the heart and is associated with a poorly understood chronic systemic inflammatory state. Interleukin 33 (IL-33) binds to membrane-bound ST2 (ST2L) and has antihypertrophic and antifibrotic effects in the myocardium. In contrast, soluble ST2 appears to act as a decoy receptor for IL-33, blocking myocardial and vascular benefits, and is a prognostic biomarker in patients with cardiovascular diseases. Here we report that a highly local intramyocardial IL-33/ST2 conversation regulates the heart's response to pressure overload. Either endothelial-specific deletion of IL33 or cardiomyocyte-specific deletion of ST2 exacerbated cardiac hypertrophy with pressure overload. Furthermore, pressure overload induced systemic circulating IL-33 as well as systemic circulating IL-13 and TGF-beta1; this was abolished by endothelial-specific deletion of IL33 but not by cardiomyocyte-specific deletion of IL33. Our study reveals that endothelial cell secretion of IL-33 is crucial for translating myocardial pressure overload into a selective systemic inflammatory response.H ypertension is the most common cardiovascular risk factor and contributes to widespread morbidity and mortality worldwide (1), but the pathological and molecular mechanisms by which elevated blood pressure promotes vascular disease remain uncertain. Inflammation has been hypothesized to play a role in hypertension as well as the progression of vascular disease (2, 3). Although the association between hypertension and inflammation has now been clearly demonstrated, molecular mechanisms that link hypertension to systemic inflammation are unclear.The soluble receptor ST2 is a prognostic biomarker in patients with cardiovascular disease (4, 5), and serum ST2 levels also predict changes in blood pressure in the community (6). ST2, also known as IL1RL1 (IL-1 receptor like 1), is a member of the IL-1 receptor family, which plays a major role in immune and inflammatory responses (7). At least two forms of ST2 are known, including the transmembrane receptor (ST2L) and the soluble form (sST2) that circulates in blood (8). Membrane-bound ST2L interacts with IL-33, an IL-1 family ligand (9), and IL-33 can have antihypertrophic and antifibrotic effects in the myocardium (10). In contrast, sST2 appears to act as a decoy receptor for IL-33, blocking myocardial and vascular benefits (10-12). IL-33 is also expressed in endothelial cells (ECs) (13-16), in which it induces angiogenesis (17), expression of adhesion molecules, and inflammatory activation (18). Here we report the surprising finding that endothelial IL-33 from pressure overload induces a selective systemic response, potentially linking hypertension with circulating factors that can affect the vasculature and other organs. Results ST2 Deficiency Exacerbates Pressure Overload-Induced CardiacHypertrophy. Communication between cardiomyocytes, fibroblasts, and ECs is important for normal cardiac function as well as pathophysiology (19,20). We explored intercellular communication in...

scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.

Contact Info

customersupport@researchsolutions.com

10624 S. Eastern Ave., Ste. A-614

Henderson, NV 89052, USA

Product

Browser Extension Assistant by scite Citation Statement Search Reference Check Visualizations Dashboards Explore Journals Explore Organizations Explore Funders Embedding Badge Embedding Citation Search Pricing

Resources

Blog Help & FAQ Accessibility Statement API Terms For Universities & Governments For Researchers For Publishers For Corporate, Pharma & Enterprise Author Marketing Become an Affiliate Get an organization trial or quote scite Data & Services

About

News & Press Careers Read our Paper Coverage

This site is protected by reCAPTCHA and the Google Privacy Policy and Terms of Service apply.

Blog Terms and Conditions API Terms Privacy Policy Contact Cookie Preferences Do Not Sell or Share My Personal Information

Copyright © 2024 scite LLC. All rights reserved.

Made with 💙 for researchers

Part of the Research Solutions Family.