Recent Advances on the Role of Cytokines in Atherosclerosis

Ait‐Oufella, Hafid; Taleb, Soraya; Mallat, Ziad; Tedgui, Alain

doi:10.1161/atvbaha.110.207415

Cited by 505 publications

(420 citation statements)

References 152 publications

Supporting

Mentioning

390

Contrasting

Unclassified

Order By: Relevance

“…We selected several proinflammatory molecules considered to be representative inflammatory mediators involved in atherogenesis to test this hypothesis 8, 9, 10. 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.…”

Section: Discussionmentioning

confidence: 99%

“…Similar to IL‐1 β , TNF‐ α is a key cytokine for the recruitment and activation of inflammatory cells 9. In addition to its known ability to alter endothelial functions and increase the extent of necrosis in advanced atherosclerotic lesions,9, 21, 22 TNF‐ α is also a potent stimulator of MMP 23. MMP‐9 is a member of the gelatinase class of the metalloproteinase family and is known to play an important role in several stages of atherosclerosis 24.…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Inflammatory mediator expression within retrieved clots in acute ischemic stroke

Baek

Kim

Yoon

et al. 2018

Ann Clin Transl Neurol

View full text Add to dashboard Cite

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.

show abstract

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Inflammatory mediator expression within retrieved clots in acute ischemic stroke

Baek

Kim

Yoon

et al. 2018

Ann Clin Transl Neurol

View full text Add to dashboard Cite

show abstract

“…11 It has been demonstrated to be proatherogenic through multiple biologic effects including influences on the endothelium (producing endothelial dysfunction), SMC apoptosis, and atherosclerotic plaque destabilization through extracellular matrix remodeling. 12,13 Although TNF-a and pro-inflammatory mediators have been found to be upregulated after cerebrovascular injury 1 and ischemia, 3,14 a potential direct role for TNF-a in SMC phenotypic modulation has not been investigated.…”

Section: Introductionmentioning

confidence: 99%

TNF-α Induces Phenotypic Modulation in Cerebral Vascular Smooth Muscle Cells: Implications for Cerebral Aneurysm Pathology

Ali

Starke

Jabbour

et al. 2013

J Cereb Blood Flow Metab

139

107

View full text Add to dashboard Cite

Little is known about vascular smooth muscle cell (SMC) phenotypic modulation in the cerebral circulation or pathogenesis of intracranial aneurysms. Tumor necrosis factor-alpha (TNF-a) has been associated with aneurysms, but potential mechanisms are unclear. Cultured rat cerebral SMCs overexpressing myocardin induced expression of key SMC contractile genes (SM-a-actin, SM-22a, smooth muscle myosin heavy chain), while dominant-negative cells suppressed expression. Tumor necrosis factor-alpha treatment inhibited this contractile phenotype and induced pro-inflammatory/matrix-remodeling genes (monocyte chemoattractant protein-1, matrix metalloproteinase-3, matrix metalloproteinase-9, vascular cell adhesion molecule-1, interleukin-1 beta). Tumor necrosis factor-alpha increased expression of KLF4, a known regulator of SMC differentiation. Kruppel-like transcription factor 4 (KLF4) small interfering RNA abrogated TNF-a activation of inflammatory genes and suppression of contractile genes. These mechanisms were confirmed in vivo after exposure of rat carotid arteries to TNF-a and early on in a model of cerebral aneurysm formation. Treatment with the synthesized TNF-a inhibitor 3,6-dithiothalidomide reversed pathologic vessel wall alterations after induced hypertension and hemodynamic stress. Chromatin immunoprecipitation assays in vivo and in vitro demonstrated that TNFa promotes epigenetic changes through KLF4-dependent alterations in promoter regions of myocardin, SMCs, and inflammatory genes. In conclusion, TNF-a induces phenotypic modulation of cerebral SMCs through myocardin and KLF4-regulated pathways. These results demonstrate a novel role for TNF-a in promoting a pro-inflammatory/matrix-remodeling phenotype, which has important implications for the mechanisms behind intracranial aneurysm formation.

show abstract

“…IL-1 and TNF signalling is primarily mediated by p38 mitogen-activated protein kinase (MAPK) / nuclear factor (NF)-κB pathways 120 . Conversely, activation of IL-6 signals via signal transducing protein gp130, which activates JAK1 and STAT1 and 3 121 resulting in the activation of endothelial cells and macrophages to produce adhesion molecules and chemokines 122 .…”

Section: Atherosclerosis Pathogenesismentioning

confidence: 99%

Erratum: Inflammatory processes in cardiovascular disease: a route to targeted therapies

Ruparelia¹,

Chai²,

Fisher³

et al. 2017

Nat Rev Cardiol

193

View full text Add to dashboard Cite

Inflammatory processes are firmly established as central to the development and complications of cardiovascular diseases. Elevated levels of inflammatory markers have been shown to be predictive of future cardiovascular events. The specific targeting of these processes in experimental models has been shown to attenuate myocardial and arterial injury, reduce disease progression, and promote healing. However, the translation of these observations and the demonstration of clear efficacy in clinical practice have been disappointing. A major limitation might be that tools currently used to measure 'inflammation' are insufficiently precise and do not provide information about disease site, activity, or discriminate between functionally important activation pathways. The challenge, therefore, is to make measures of inflammation that are more meaningful, and which can guide specific targeted therapies. In this Review, we consider the roles of inflammatory processes in the related pathologies of atherosclerosis and acute myocardial infarction (AMI), by providing an evaluation of the known and emerging inflammatory pathways. We highlight contemporary techniques to characterize and quantify inflammation, and consider how they might be used to guide specific treatments. Finally, we discuss emerging opportunities in the field, including current limitations and challenges that are the focus of ongoing study.Inflammation and its failure to resolve are firmly established as central to the development and complications of several cardiovascular diseases [1][2][3] . Elevated levels of markers of inflammation, such as C-reactive protein (CRP) and serum amyloid A (SAA), have been shown to be predictive of future cardiovascular events across a range of clinical settings [4][5][6] . The role of the innate immune system in the pathogenesis of cardiovascular diseases has been an area of particular focus, with the appreciation that targeting innate immune function Correspondence to R.P.C.: robin.choudhury@cardiov.ox.ac.uk. Author contributionsAll the authors researched data for the article, discussed its contents, and wrote, reviewed, and edited the manuscript before submission. Competing interests statementThe authors declare no competing interests. HHS Public AccessAuthor manuscript Nat Rev Cardiol. Author manuscript; available in PMC 2017 September 01. Author Manuscript Author ManuscriptAuthor ManuscriptAuthor Manuscript in experimental models can variously attenuate disease progression and injury, and promote healing [7][8][9][10] .Processes of inflammation contribute to a broad range of cardiovascular diseases; however, in this Review, we consider the roles of inflammatory processes in the related pathologies of atherosclerosis and acute myocardial infarction (AMI), by providing an evaluation of known and emerging inflammatory pathways that are thought to be central to their pathogenesis, and the consequences of their activation. We highlight contemporary techniques to characterize and quantify inflammation, and consider h...

show abstract

Recent Advances on the Role of Cytokines in Atherosclerosis

Cited by 505 publications

References 152 publications

Inflammatory mediator expression within retrieved clots in acute ischemic stroke

Inflammatory mediator expression within retrieved clots in acute ischemic stroke

TNF-α Induces Phenotypic Modulation in Cerebral Vascular Smooth Muscle Cells: Implications for Cerebral Aneurysm Pathology

Erratum: Inflammatory processes in cardiovascular disease: a route to targeted therapies

Contact Info

Product

Resources

About