Atherosclerosis induced by endogenous and exogenous toll-like receptor (TLR)1 or TLR6 agonists

Curtiss, Linda K.; Black, Audrey S.; Bonnet, David J.; Tobias, Peter S.

doi:10.1194/jlr.m028431

Cited by 50 publications

(51 citation statements)

References 19 publications

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“…186,209 The stimulation of TLRs might ultimately induce the activation of IRFs via multistage factors, eg, MyD88, tripartite motif, TRAF, A20, and IKKs, in various cell types, including macrophages, DCs, endothelial cells, and SMCs, that participate in the progression of atherosclerosis. 210 Accumulating studies using murine models focusing on the regulation of atherosclerosis by TLRs have deduced a phenomenon in which extracellular TLRs, including TLR1, 211 215 Early studies of the impact of TRAFs on atherogenesis have indicated that the expression levels of TRAF1, TRAF2, TRAF3, and TRAF6 were significantly increased by the activation of CD40 signaling, 216 a molecular program that is significantly involved in atherosclerosis. 215 Additional studies revealed that the downregulation of TRAF1, TRAF3, or TRAF6 markedly increased the CD40 ligand-induced inflammatory response, whereas the silencing of TRAF2 and TRAF5 retarded vascular endothelial inflammation.…”

Section: Upstream Irf Signaling In Vascular Injurymentioning

confidence: 99%

Interferon Regulatory Factor Signalings in Cardiometabolic Diseases

Zhang

2015

Hypertension

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Section: Upstream Irf Signaling In Vascular Injurymentioning

confidence: 99%

Interferon Regulatory Factor Signalings in Cardiometabolic Diseases

Zhang

2015

Hypertension

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“…Although treatment of high-fat diet-fed LDLR −/− mice with the exogenous TLR2/TLR1 ligand Pam3CysK4 and exogenous TLR2/TLR6 ligand MALP-2 increased atherosclerotic lesion development in a TLR1-and TLR6-dependent manner, respectively; no difference in only high-fat diet-induced lesion size between LDLR −/− TLR1 −/− mice and LDLR −/− TLR6 −/− mice versus LDLR −/− mice was observed. 164 This suggests that engagement of TLR1 and TLR6 is either redundant or, as opposed to TLR2, does not play a significant role in the context of diet-induced murine atherosclerosis.…”

Section: Toll-like Receptorsmentioning

confidence: 99%

“…165 Adenoviral transfer of a dominant-negative form of MyD88 and TLR2-blocking antibodies led to decreased production of proinflammatory factors, chemokines and various proteases in atheroma cell cultures, whereas IL-1 receptor antagonist (IL-1Ra), TLR4-blocking antibodies, or overexpression of a dominant-negative form of TRIF did not affect the production of the mediators studied. 164 Local arterial TLR2 stimulation induced neointima and atherosclerotic plaque formation in mouse femoral arteries. 166 Moreover, HDL from patients with chronic kidney disease as opposed to HDL from healthy volunteers is modified by an endogenous proinflammatory trigger, symmetrical dimethylarginine, that can induce proatherogenic pathways via TLR2.…”

Section: Toll-like Receptorsmentioning

confidence: 99%

Danger Signaling in Atherosclerosis

Zimmer

Grebe

Latz

2015

Circulation Research

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All aspects of the pathogenesis of atherosclerosis are critically influenced by the inflammatory response in vascular plaques. Research in the field of innate immunity from the past 2 decades has uncovered many novel mechanisms elucidating how immune cells sense microbes, tissue damage, and metabolic derangements. Here, we summarize which triggers of innate immunity appear during atherogenesis and by which pathways they can contribute to inflammation in atherosclerotic plaques. The increased understanding gained from studies assessing how immune activation is associated with the pathogenesis of atherosclerosis has provided many novel targets for potential therapeutic intervention. Excitingly, the concept that inflammation may be the core of cardiovascular disease is currently being clinically evaluated and will probably encourage further studies in this area.

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“…However, exogenous ligands promote a severe abdominal atherosclerosis that is dependent on TLR1 and TLR6. Thus, when hypercholesterolemia is combined with sources of inflammation external to the vessel wall, arterial lesions are complicated [130]. These exacerbated responses, mediated by pathogens, explain the increased number of cardiovascular events that occur during different infectious process.…”

Section: How Risk Factors and Comorbidities Could Cooperate With Ox-lmentioning

confidence: 99%

Are oxidised low-density lipoproteins the true inducers of inflammation in atherosclerosis?

Montero-Vega¹

2014

Inflammasome

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Low-density lipoproteins become oxidised (ox-LDL) when retained in the arterial intima and are considered to be the inducers of inflammation in atherosclerosis. Peroxidation of phospholipids generates a variety of oxidised molecules in LDL and leads to the formation of oxidised lipid-protein adducts. These oxidative modifications are the target of various pattern recognition receptors (PRRs) and constitute immunogenic neoepitopes, termed oxidation-specific epitopes (OSEs). OSEs are thought to be a class of danger-associated molecular patterns (DAMPs) that mediate pro-inflammatory signals in atherosclerosis. Nevertheless, identical OSEs are generated on apoptotic cells that are identified by innate immunity through the same receptors to promote housekeeping tasks and immunosuppression. The present study provides an alternative point of view and proposes that OSEs are ‘waste-associated molecular patterns’ (WAMPs) recognised by innate immunity as a signal for the presence of oxidised waste that must be cleared without triggering inflammation. The hypothesis presented here states that ox-LDL are not inflammatory per se but instead polarise macrophages for housekeeping functions; however, other immune alerts, which are generated under the influence of risk factors, cooperate with them in switching macrophage polarisation towards dangerous phenotypes that complicate atheromas with different tendencies. This hypothesis of ‘immune cooperation’ explains why atheromas grow silently for decades and reveals atherosclerosis to be a dynamic disease that begins with the retention and oxidation of LDL in the arterial intima and ends with the formation of a thrombus, but in which the underlying immune process changes over time and differs between patients.

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Atherosclerosis induced by endogenous and exogenous toll-like receptor (TLR)1 or TLR6 agonists

Cited by 50 publications

References 19 publications

Interferon Regulatory Factor Signalings in Cardiometabolic Diseases

Interferon Regulatory Factor Signalings in Cardiometabolic Diseases

Danger Signaling in Atherosclerosis

Are oxidised low-density lipoproteins the true inducers of inflammation in atherosclerosis?

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