Interleukin-1 plays a major role in vascular inflammation and atherosclerosis in male apolipoprotein E-knockout mice

Merhi-Soussi, Faten; Kwak, Brenda R.; Magne, David; Chadjichristos, Christos; Berti, Marina; Pelli, Graziano; James, Richard; Mach, François; Gabay, Cem

doi:10.1016/j.cardiores.2005.01.008

Cited by 191 publications

(135 citation statements)

References 33 publications

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“…MOS did not affect specific markers of systemic inflammation associated with atherosclerosis,31 despite having anti‐inflammatory properties in previous studies 11, 12, 13. However, we cannot exclude the possibility that MOS might have modulated other systemic immune markers or that it has affected the immune status more subtly or locally, for example within the atherosclerotic plaque.…”

Section: Discussionmentioning

confidence: 63%

Dietary Mannan Oligosaccharides Modulate Gut Microbiota, Increase Fecal Bile Acid Excretion, and Decrease Plasma Cholesterol and Atherosclerosis Development

Hoving

Katiraei

Heijink

et al. 2018

Molecular Nutrition Food Res

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ScopeMannan oligosaccharides (MOS) have proven effective at improving growth performance, while also reducing hyperlipidemia and inflammation. As atherosclerosis is accelerated both by hyperlipidemia and inflammation, we aim to determine the effect of dietary MOS on atherosclerosis development in hyperlipidemic ApoE*3‐Leiden.CETP (E3L.CETP) mice, a well‐established model for human‐like lipoprotein metabolism.Methods and resultsFemale E3L.CETP mice were fed a high‐cholesterol diet, with or without 1% MOS for 14 weeks. MOS substantially decreased atherosclerotic lesions up to 54%, as assessed in the valve area of the aortic root. In blood, IL‐1RA, monocyte subtypes, lipids, and bile acids (BAs) were not affected by MOS. Gut microbiota composition was determined using 16S rRNA gene sequencing and MOS increased the abundance of cecal Bacteroides ovatus. MOS did not affect fecal excretion of cholesterol, but increased fecal BAs as well as butyrate in cecum as determined by gas chromatography mass spectrometry.ConclusionMOS decreased the onset of atherosclerosis development via lowering of plasma cholesterol levels. These effects were accompanied by increased cecal butyrate and fecal excretion of BAs, presumably mediated via interactions of MOS with the gut microbiota.

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Section: Discussionmentioning

confidence: 63%

Dietary Mannan Oligosaccharides Modulate Gut Microbiota, Increase Fecal Bile Acid Excretion, and Decrease Plasma Cholesterol and Atherosclerosis Development

Hoving

Katiraei

Heijink

et al. 2018

Molecular Nutrition Food Res

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“…IL-1RI deficiency diminished aortic lesions, whereas IL-1RA deficiency exacerbated them, in ApoE-deficient mice fed high fat/high cholesterol "Western" diets, suggesting that IL-1RA tonically opposes a contributing role of endogenous IL-1 (acting via IL-1RI) in such lesion formation (18). IL-1RI deficiency also reduced aortic lesions in mice infected systemically with Porphyromonas gingivalis, a periodontal pathogen, indicating a mediating role of IL-1RI in microbially induced vasculopathy (8).…”

Section: Discussionmentioning

confidence: 99%

Endogenous interleukin-1α promotes a proliferative and proinflammatory phenotype in human vascular smooth muscle cells

Schultz

Murthy²,

Tatro³

et al. 2007

American Journal of Physiology-Heart and Circulatory Physiology

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Schultz K, Murthy V, Tatro JB, Beasley D. Endogenous interleukin-1␣ promotes a proliferative and proinflammatory phenotype in human vascular smooth muscle cells. Am J Physiol Heart Circ Physiol 292: H2927-H2934, 2007. First published February 9, 2007 doi:10.1152/ajpheart.00700.2006.-During vascular disease and following injury, vascular smooth muscle cells (VSMC) proliferate and produce inflammation-promoting cytokines and chemokines. Similar phenotypic changes can be elicited in vitro by activation of Toll-like receptors (TLR) within VSMC. TLR-activated VSMC also produce IL-1␣, but it is unknown whether endogenous IL-1␣ stimulates VSMC in an autocrine manner. Here we tested the hypothesis that endogenous IL-1␣ contributes to TLR-induced proliferation and chemokine release in human VSMC by using RNA interference to knock down IL-1␣ expression. Knockdown of IL-1␣ abolished TLR-induced proliferation and suppressed TLR4-induced release of monocyte chemoattractant protein-1 (MCP-1) by VSMC, indicating that endogenous IL-1␣ plays a crucial role in both responses. Serum, PDGF, FGF-2, and EGF each increased cellular IL-1␣ concentrations, and IL-1␣ knockdown inhibited serum-and PDGF-induced DNA synthesis, further indicating that endogenous IL-1␣ also contributed to VSMC responses to growth factors. IL-1 receptor antagonist, a competitive inhibitor of IL-1 receptor I (IL-1RI), also attenuated TLRinduced proliferation and both basal and TLR-induced MCP-1 expression, indicating at least a partial role of the IL-1RI in mediating these responses. The results support the hypothesis that autocrine actions of endogenous IL-1␣, mediated at least in part via IL-1RI signaling, contribute to a proproliferative and proinflammatory phenotypic shift in TLR-activated human VSMC, which might play a pathogenic role in vascular disorders. monocyte chemoattractant protein-1; cell proliferation; type I interleukin-1 receptor EXCESSIVE PROLIFERATION OF vascular smooth muscle cells (VSMC) is a prototypical response to vascular injury and is also a feature of early-stage atherogenesis. Such proliferative responses of VSMC may contribute to vascular repair in some cases, but they can also lead to restenosis when excessive (1). Another fundamental and dramatic change displayed by VSMC following either vascular injury or chronic exposure to intravascular lipids is their shift to a proinflammatory phenotype, characterized by the synthesis of proinflammatory cytokines and chemokines, including interleukin-1␣ (IL-1␣) and monocyte chemoattractant protein-1 (MCP-1) (7,9,22,29). The functions of endogenous VSMC-derived IL-1␣ in this context are unknown, but we have hypothesized that it may play an autocrine role in promoting VSMC proliferation, based on in vitro and in vivo lines of evidence. For example, in coronary bypass patients, IL-1␣ was found in spindle-shaped cells within saphenous vein grafts that had become stenotic but not in those that remained patent (5). Similarly, IL-1␣ mRNA was found in medial smooth muscle cells (SMC) within arterial ...

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“…Of these selected mediators, we observed that IL‐1 β expression was significantly higher in clots from patients with large artery atherosclerosis than in those with either cardioembolism or undetermined etiology. IL‐1 is a prototypic proinflammatory cytokine that leads to the recruitment of inflammatory cells by inducing the production of cytokines and chemokines and increasing the expression of adhesion molecules on endothelial cells 18. The term IL‐1 refers to two distinct but related proteins, IL‐1 α and IL‐1 β .…”

Section: Discussionmentioning

confidence: 99%

Inflammatory mediator expression within retrieved clots in acute ischemic stroke

Baek

Kim

Yoon

et al. 2018

Ann Clin Transl Neurol

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ObjectiveIn this study we investigate the association between the expression of inflammatory mediators measured in clots retrieved by mechanical thrombectomy, stroke etiology, and the susceptibility vessel sign (SVS) on gradient‐echo (GRE) MR imaging in acute ischemic stroke patients.MethodsWe performed molecular analysis of intracranial clots retrieved by mechanical thrombectomy from 82 patients with acute stroke. Seventy‐two of these patients underwent GRE imaging before endovascular therapy. We measured the relative expression of inflammatory mediators by performing the quantitative real‐time polymerase chain reaction on the retrieved clots and assessed associations between the expression of inflammatory mediators and stroke subtypes as well as with GRE SVS.ResultsClassifications of stroke etiology for the cohort were as follows: cardioembolism (51, 62.2%), large artery atherosclerosis (9, 11%), and undetermined etiology (22, 26.8%). Clots associated with large artery atherosclerosis showed significantly higher interleukin (IL)‐1β expression than clots from both cardioembolism and undetermined etiology (P = 0.008). A positive SVS was identified in 48 of 72 patients (66.7%) who had GRE imaging. IL‐1β, tumor necrosis factor‐α, and matrix metalloproteinase‐9 expressions were significantly higher in clots with a negative SVS than in those with a positive SVS (P = 0.010, 0.049, and 0.004, respectively).InterpretationExpression of inflammatory mediators in intracranial clots differs significantly based on stroke etiology or presence or the absence of SVS on GRE imaging. This study suggests that molecular analysis of inflammatory mediators in retrieved clots is a promising tool for determining stroke mechanism in acute ischemic stroke patients.

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Interleukin-1 plays a major role in vascular inflammation and atherosclerosis in male apolipoprotein E-knockout mice

Abstract: Our results demonstrate that the IL-1/IL-1Ra ratio plays a critical role in the pathogenic mechanisms leading to vascular inflammation and atherosclerosis in ApoE -/- mice.

Cited by 191 publications

References 33 publications

Dietary Mannan Oligosaccharides Modulate Gut Microbiota, Increase Fecal Bile Acid Excretion, and Decrease Plasma Cholesterol and Atherosclerosis Development

Dietary Mannan Oligosaccharides Modulate Gut Microbiota, Increase Fecal Bile Acid Excretion, and Decrease Plasma Cholesterol and Atherosclerosis Development

Endogenous interleukin-1α promotes a proliferative and proinflammatory phenotype in human vascular smooth muscle cells

Inflammatory mediator expression within retrieved clots in acute ischemic stroke

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