Identification of foam cell biomarkers by microarray analysis

Song, Zikai; Lv, Shanshan; Wu, Haidi; Qin, Ling; Cao, Hongyan; Zhang, Bo; Ren, Shuping

doi:10.1186/s12872-020-01495-0

Cited by 8 publications

(5 citation statements)

References 42 publications

(34 reference statements)

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“…We also observed the induction of genes encoding secreted pro-inflammatory mediators, mainly chemokines, such as CXCL7 (also named pro-platelet basic protein , PPBP ), CLL7 , CXCL5 and CXCL8 . CXCL7/PPBP is a fatty acid-induced chemokine elevated in atherosclerosis; CCL7 is a macrophage foam cell marker [ 30 ] recruiting monocytes to sites of inflammation and has a high affinity to CCR2. CXCL5 is a chemokine regulating macrophage cholesterol efflux as well as tissue remodelling/invasion.…”

Section: Resultsmentioning

confidence: 99%

Saturated very long-chain fatty acids regulate macrophage plasticity and invasiveness

Zierfuss

Buda

Villoria-González

et al. 2022

J Neuroinflammation

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Saturated very long-chain fatty acids (VLCFA, ≥ C22), enriched in brain myelin and innate immune cells, accumulate in X-linked adrenoleukodystrophy (X-ALD) due to inherited dysfunction of the peroxisomal VLCFA transporter ABCD1. In its severest form, X-ALD causes cerebral myelin destruction with infiltration of pro-inflammatory skewed monocytes/macrophages. How VLCFA levels relate to macrophage activation is unclear. Here, whole transcriptome sequencing of X-ALD macrophages indicated that VLCFAs prime human macrophage membranes for inflammation and increased expression of factors involved in chemotaxis and invasion. When added externally to mimic lipid release in demyelinating X-ALD lesions, VLCFAs did not activate toll-like receptors in primary macrophages. In contrast, VLCFAs provoked pro-inflammatory responses through scavenger receptor CD36-mediated uptake, cumulating in JNK signalling and expression of matrix-degrading enzymes and chemokine release. Following pro-inflammatory LPS activation, VLCFA levels increased also in healthy macrophages. With the onset of the resolution, VLCFAs were rapidly cleared in control macrophages by increased peroxisomal VLCFA degradation through liver-X-receptor mediated upregulation of ABCD1. ABCD1 deficiency impaired VLCFA homeostasis and prolonged pro-inflammatory gene expression upon LPS treatment. Our study uncovers a pivotal role for ABCD1, a protein linked to neuroinflammation, and associated peroxisomal VLCFA degradation in regulating macrophage plasticity.

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Section: Resultsmentioning

confidence: 99%

Saturated very long-chain fatty acids regulate macrophage plasticity and invasiveness

Zierfuss

Buda

Villoria-González

et al. 2022

J Neuroinflammation

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“…Hence, it can be concluded that SPI1 could be the crucial TF regulating the two crosstalk genes in HAP. Due to cytokines interleukin-1β (IL-1β) is considered to be the key mediators of HAP ( 49 ), and lipid metabolism related genes, such as ABCG1, etc., were the key to the transformation of macrophages into foam cells ( 50 ), hence we examined the expression levels of IL-1β, CXCL1, CCL3, CCL4, and ABCG1 in the three GEO datasets. Figures 10E–I shows that the expression levels of IL-1β, CXCL1, CCL3, CCL4, and ABCG1 were upregulated in all three GEO datasets.…”

Section: Resultsmentioning

confidence: 99%

An integrative analysis of single-cell and bulk transcriptome and bidirectional mendelian randomization analysis identified C1Q as a novel stimulated risk gene for Atherosclerosis

Cui,

Tang,

Gao

et al. 2023

Front. Immunol.

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BackgroundThe role of complement component 1q (C1Q) related genes on human atherosclerotic plaques (HAP) is less known. Our aim is to establish C1Q associated hub genes using single-cell RNA sequencing (scRNA-seq) and bulk RNA analysis to diagnose and predict HAP patients more effectively and investigate the association between C1Q and HAP (ischemic stroke) using bidirectional Mendelian randomization (MR) analysis.MethodsHAP scRNA-seq and bulk-RNA data were download from the Gene Expression Omnibus (GEO) database. The C1Q-related hub genes was screened using the GBM, LASSO and XGBoost algorithms. We built machine learning models to diagnose and distinguish between types of atherosclerosis using generalized linear models and receiver operating characteristics (ROC) analyses. Further, we scored the HALLMARK_COMPLEMENT signaling pathway using ssGSEA and confirmed hub gene expression through qRT-PCR in RAW264.7 macrophages and apoE-/- mice. Furthermore, the risk association between C1Q and HAP was assessed through bidirectional MR analysis, with C1Q as exposure and ischemic stroke (IS, large artery atherosclerosis) as outcomes. Inverse variance weighting (IVW) was used as the main method.ResultsWe utilized scRNA-seq dataset (GSE159677) to identify 24 cell clusters and 12 cell types, and revealed seven C1Q associated DEGs in both the scRNA-seq and GEO datasets. We then used GBM, LASSO and XGBoost to select C1QA and C1QC from the seven DEGs. Our findings indicated that both training and validation cohorts had satisfactory diagnostic accuracy for identifying patients with HPAs. Additionally, we confirmed SPI1 as a potential TF responsible for regulating the two hub genes in HAP. Our analysis further revealed that the HALLMARK_COMPLEMENT signaling pathway was correlated and activated with C1QA and C1QC. We confirmed high expression levels of C1QA, C1QC and SPI1 in ox-LDL-treated RAW264.7 macrophages and apoE-/- mice using qPCR. The results of MR indicated that there was a positive association between the genetic risk of C1Q and IS, as evidenced by an odds ratio (OR) of 1.118 (95%CI: 1.013–1.234, P = 0.027).ConclusionThe authors have effectively developed and validated a novel diagnostic signature comprising two genes for HAP, while MR analysis has provided evidence supporting a favorable association of C1Q on IS.

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“…Furthermore, HMGCR and HMGCS1 are key genes in promoting macrophage foam cell formation. Increased activity of HMGCR and HMGCS1 contributes to excessive activation of the cholesterol synthesis pathway, which in turn leads to macrophage lipid droplet formation ( 33 ). Therefore, Mtb-induced overexpression of HMGCR and HMGCS1 may inhibit phagocytic activity of macrophages, promote cholesterol accumulation and foam cell formation, and even cause macrophage death.…”

Section: The Effect Of Mtb Infection On Macrophage Cholesterol Metabo...mentioning

confidence: 99%

“…DHCR24, also known as 3β-hydroxysterol Δ24-reductase, is a human flavin adenine dinucleotide (FAD)-dependent oxidoreductase that catalyzes the final step of cholesterol synthesis, converting desmosterol to cholesterol ( 36 ). In addition to HMGCR and HMGCS1, DHCR24 is also a key gene in promoting macrophage foam cell formation and possesses antioxidant functions that effectively inhibit oxidative stress ( 33 , 37 ). Consequently, Mtb infection of macrophages may elevate immune inflammation levels, inhibit oxidative stress, and induce cholesterol accumulation as well as foam cell formation by upregulating MVD and DHCR24 expression.…”

Section: The Effect Of Mtb Infection On Macrophage Cholesterol Metabo...mentioning

confidence: 99%

The impact of Mycobacterium tuberculosis on the macrophage cholesterol metabolism pathway

Chen,

Kong,

et al. 2024

Front. Immunol.

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Mycobacterium tuberculosis (Mtb) is an intracellular pathogen capable of adapting and surviving within macrophages, utilizing host nutrients for its growth and replication. Cholesterol is the main carbon source during the infection process of Mtb. Cholesterol metabolism in macrophages is tightly associated with cell functions such as phagocytosis of pathogens, antigen presentation, inflammatory responses, and tissue repair. Research has shown that Mtb infection increases the uptake of low-density lipoprotein (LDL) and cholesterol by macrophages, and enhances de novo cholesterol synthesis in macrophages. Excessive cholesterol is converted into cholesterol esters, while the degradation of cholesterol esters in macrophages is inhibited by Mtb. Furthermore, Mtb infection suppresses the expression of ATP-binding cassette (ABC) transporters in macrophages, impeding cholesterol efflux. These alterations result in the massive accumulation of cholesterol in macrophages, promoting the formation of lipid droplets and foam cells, which ultimately facilitates the persistent survival of Mtb and the progression of tuberculosis (TB), including granuloma formation, tissue cavitation, and systemic dissemination. Mtb infection may also promote the conversion of cholesterol into oxidized cholesterol within macrophages, with the oxidized cholesterol exhibiting anti-Mtb activity. Recent drug development has discovered that reducing cholesterol levels in macrophages can inhibit the invasion of Mtb into macrophages and increase the permeability of anti-tuberculosis drugs. The development of drugs targeting cholesterol metabolic pathways in macrophages, as well as the modification of existing drugs, holds promise for the development of more efficient anti-tuberculosis medications.

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Identification of foam cell biomarkers by microarray analysis

Cited by 8 publications

References 42 publications

Saturated very long-chain fatty acids regulate macrophage plasticity and invasiveness

Saturated very long-chain fatty acids regulate macrophage plasticity and invasiveness

An integrative analysis of single-cell and bulk transcriptome and bidirectional mendelian randomization analysis identified C1Q as a novel stimulated risk gene for Atherosclerosis

The impact of Mycobacterium tuberculosis on the macrophage cholesterol metabolism pathway

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