Is Toll-like receptor responsiveness a marker and predictor of coronary artery disease?

Björkbacka, Harry

doi:10.1016/j.atherosclerosis.2013.11.032

Cited by 4 publications

(3 citation statements)

References 16 publications

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“…It has been reported that mTOR signaling pathway plays an important role in monocyte proinflammatory response in patients with CAD [ 23 ]. The Toll-like receptor signaling has been shown to be involved in the pathogenesis of CAD [ 24 , 25 ]. Recently, Toll-like receptor signaling pathway, and NOD-like receptor signaling pathway associated with inflammation may be involved in regulating the progression of CAD [ 26 ].…”

Section: Discussionmentioning

confidence: 99%

Construction and validation of molecular subtypes of coronary artery disease based on ferroptosis-related genes

Ding¹,

Long²,

An³

et al. 2022

BMC Cardiovasc Disord

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Background This study aims to construct a reliable diagnostic model for coronary artery disease (CAD) patients and explore its potential mechanism by consensus molecular subtypes of ferroptosis-related genes. Methods GSE12288 and GSE20680 were downloaded from Gene Expression Omnibus database. CAD patients were divided into different molecular subtypes according to the expression level of ferroptosis-related genes. Then, the distribution of differentially expressed genes, functional annotations and immune infiltration cells between the two subtypes were compared. Finally, a prognostic model of ferroptosis-related genes in CAD was constructed and verified. Results Two different molecular subtypes of CAD were obtained according to the expression level of ferroptosis-related genes. Then, a total of 1944 differentially expressed genes (DEGs) were found, among which, 236 genes were up-regulated and 1708 genes were down-regulated. In addition, 43 DEGs were ferroptosis-related genes. Functional enrichment analysis showed that these DEGs between two subtypes of CAD were mainly enriched in immune-related pathways and processes, such as T cell receptor, mTOR, NOD-like receptor and Toll-like receptor signaling pathways. We also found that 21 immune cells were significantly changed between two subtypes of CAD. The LASSO method was performed to identify and construct the 16 ferroptosis-related genes-based diagnostic signature. Diagnostic efficiency of diagnostic signature measured by AUC in the training set and validation cohort was 0.971 and 0.899, respectively. Conclusions This study contributes to a more comprehensive understanding of the mechanism of ferroptosis-related genes in CAD.

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Section: Discussionmentioning

confidence: 99%

Construction and validation of molecular subtypes of coronary artery disease based on ferroptosis-related genes

Ding¹,

Long²,

An³

et al. 2022

BMC Cardiovasc Disord

View full text Add to dashboard Cite

show abstract

“…[ 13 ] Epidemiological studies suggest a strong association between inflammation and arterial disease. [ 2 4 5 21 ] The inflammatory reaction in blood vessels contributes a crucial role in the progression of atherosclerosis until the precipitation of clinical symptoms such as myocardial infarction and stroke. [ 12 ] Therefore, it is very important to elucidate the molecular mechanism underlying atherosclerotic inflammation for developing potent and safe therapeutic approaches for patients with atherosclerosis.…”

Section: Discussionmentioning

confidence: 99%

Involvement of the toll-like receptors-2/nuclear factor-kappa B signaling pathway in atherosclerosis induced by high-fat diet and zymosan A in C57BL/6 mice

Arya

Bhandari

2020

Indian J Pharmacol

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OBJECTIVE: Accumulated evidence reported a link between the immune system, microbial infection, and the development of atherosclerosis. Excess intake of high-fat diet (HFD) increases blood lipid levels and induces inflammatory pathways whereas zymosan A (Zym), a microbial component, mediates inflammatory response through the stimulation of specific ligand of toll-like receptors (TLRs) of the immune system. The current research work was aimed to evaluate the mechanism behind atherosclerosis mediated by HFD and Zym in C57BL/6 mice. MATERIALS AND METHODS: The mice were orally fed with HFD for 30 days and Zym (80 mg/kg, single intraperitoneal injection on day 8 th ). On the 31 st day, blood was withdrawn from overnight fasted mice by tail vein puncture and estimated for serum lipids and tumor necrosis factor-alpha (TNF-α). Animals were sacrificed, and cardiac, liver, and aortic tissues were isolated for the estimation of cardiac TLR-2, nuclear factor-kappa B (NF-ƙB); hepatic low-density lipoprotein receptors (LDLR); and base of aorta analyzed for histopathology. RESULTS: It was found that HFD and Zym administration increased arterial inflammation directly through modulation of the TLR-2/NF-ƙB pathway, thereby upregulate serum TNF-α, cardiac TLR-2, and NF-ƙB levels. Further, HFD and Zym treatment significantly increased serum lipid levels and marked decrease in LDLR protein expression in the liver when compared to normal control mice. Histopathological analysis showed the formation of atherosclerotic plaque. CONCLUSION: The study is first, to our current knowledge, to demonstrate the involvement of the TLR-2/NF-ƙB signaling pathway in atherosclerosis induced by HFD and Zym in C57BL/6 mice, resulting in increased degradation of LDLR protein, thereby, increasing the serum lipid levels.

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“…Our data suggests that TLRs are chronically activated in cardiovascular disease, associated with a decrease in TCR and BCR expression in the peripheral blood. This expression pattern may be the result of chronic tissue damage, attempts to resolve chronic inflammation, and decreased immune system reserve [ 16 ]. A hallmark of atherosclerotic disease is the accumulation of T cells within the atherosclerotic lesion where they play a direct role in plaque rupture [ 17 ].…”

Section: Discussionmentioning

confidence: 99%

Systemic Transcriptional Alterations of Innate and Adaptive Immune Signaling Pathways in Atherosclerosis, Ischemia Stroke, and Myocardial Infarction

et al. 2015

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Background Transcriptional profiles are available for a variety of cardiovascular-related diseases. The goal of this study was to compare blood transcriptional profiles of the Toll-like receptor (TLR), T-cell receptor (TCR), and B-cell receptor (BCR) signaling pathways in asymptomatic atherosclerosis, acute ischemic stroke, and myocardial infarction patients to identify common mechanisms of immune regulation and their association with epigenetic regulation. Methods and results Peripheral blood gene expression profiles from human atherosclerosis-related diseases and healthy controls were downloaded from Gene Expression Omnibus (GEO). Genes in the TLR, TCR, and BCR pathways were retrieved from the NCBI BioSystems database. Significance of gene enrichment and concordance of expression changes in each pathway was compared between studies. Gene expression was significantly correlated across the three disease conditions (p<10−15) and the proportion of significant genes was high (30~60%, p<0.001). Hub genes identified by weighted gene co-expression network analysis (WGCNA) in the TCR/BCR sub-network, including CD81 and TCR-CD3ζ, were significantly down-regulated and highly correlated with DNA (cytosine-5-)-methyltransferase 1 (DNMT1). Conclusion Common biologically relevant networks associated with immune regulation in stroke, atherosclerosis, and myocardial infarction were discovered. Given the high correlation of DNMT1 with these immune signaling pathways, epigenetic regulation may contribute to the coordination of innate and adaptive immune response in all CVD disease states. Down-regulation of the TCR-BCR axis in the adaptive immune system offers critical information for the investigation of the functional mechanisms underlying chronic inflammation-induced immune suppression in cardiovascular disease and stroke.

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Is Toll-like receptor responsiveness a marker and predictor of coronary artery disease?

Cited by 4 publications

References 16 publications

Construction and validation of molecular subtypes of coronary artery disease based on ferroptosis-related genes

Construction and validation of molecular subtypes of coronary artery disease based on ferroptosis-related genes

Involvement of the toll-like receptors-2/nuclear factor-kappa B signaling pathway in atherosclerosis induced by high-fat diet and zymosan A in C57BL/6 mice

Systemic Transcriptional Alterations of Innate and Adaptive Immune Signaling Pathways in Atherosclerosis, Ischemia Stroke, and Myocardial Infarction

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