CTRP1 decreases ABCA1 expression and promotes lipid accumulation through the miR‐424‐5p/FoxO1 pathway in THP‐1 macrophage‐derived foam cells

Zhang, Zizhen; Chen, Jiaojiao; Deng, Wenyi; Tan, Wei-Hua

doi:10.1002/cbin.11666

Cited by 8 publications

(8 citation statements)

References 36 publications

(54 reference statements)

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“…In the present study, MSC-derived exosomal-mediated delivery of si-LOC100129516 significantly inhibited the apoptosis, intracellular cholesterol accumulation and lipid accumulation of THP-1 macrophage-derived foam cells, consistent with Meng et al (48). In the study by Meng et al (48), GAS5 knockdown reduced EZH2-mediated transcriptional inhibition of ABCA1 via histone methylation, and ABCA1 served a vital role in atherosclerotic progression (49). Consistently, ABCA1 was found to be regulated by exosomes with downregulated levels of LOC100129516.…”

Section: Discussionsupporting

confidence: 91%

Knockdown of mesenchymal stem cell‑derived exosomal LOC100129516 suppresses the symptoms of atherosclerosis via upregulation of the PPARγ/LXRα/ABCA1 signaling pathway

Zhang

Han

et al. 2021

Int J Mol Med

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Mesenchymal stem cell (MSC) therapy has potential applications in treating atherosclerosis and coronary heart disease (CAD). Previous studies have demonstrated that MSCs are the most preferable sources of therapeutic exosomes, which carry long non-coding RNAs and participate in the progression of atherosclerosis. The results of our previous bioinformatics study demonstrated that the levels of LOC100129516 were significantly upregulated in peripheral blood mononuclear cells obtained from patients with CAD. However, the biological role of LOC100129516 in the development of atherosclerosis remains to be elucidated. In the present study, THP-1 cells were treated with oxidized low-density lipoproteins to induce foam cell formation in vitro . Reverse transcription-quantitative PCR (RT-qPCR) was performed to detect the levels of LOC100129516 in THP-1 macrophage-derived foam cells. In addition, an in vivo model of atherosclerosis was established using Apolipoprotein E (ApoE) knockout (ApoE −/− ) mice. The results of the RT-qPCR assays demonstrated that the levels of LOC100129516 were upregulated in THP-1 macrophage-derived foam cells. MSC-derived exosomes were able to deliver small interfering (si)-LOC100129516 to THP-1 cells to reduce the levels of LOC100129516. Moreover, transfection of si-LOC100129516 via exosomal delivery significantly decreased the levels of total cholesterol (TC), free cholesterol and cholesterol ester in THP-1 macrophage-derived foam cells. Exosomal-mediated delivery of si-LOC100129516 decreased TC levels and low-density lipoprotein levels in the ApoE −/− atherosclerosis mouse model. Mechanistically, exosomal-mediated delivery of si-LOC100129516 promoted cholesterol efflux by activating the peroxisome proliferator-activated receptor γ (PPARγ)/liver X receptor α (LXRα)/phospholipid-transporting ATPase ABCA1 (ABCA1) signaling pathway in vitro and in vivo . Collectively, these results suggested that exosomal-mediated delivery of si-LOC100129516, in which the exosomes were derived from MSCs, promoted cholesterol efflux and suppressed intracellular lipid accumulation, ultimately alleviating the progression of atherosclerosis via stimulation of the PPARγ/LXRα/ABCA1 signaling pathway.

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Section: Discussionsupporting

confidence: 91%

Knockdown of mesenchymal stem cell‑derived exosomal LOC100129516 suppresses the symptoms of atherosclerosis via upregulation of the PPARγ/LXRα/ABCA1 signaling pathway

Zhang

Han

et al. 2021

Int J Mol Med

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“…FOXO1 plays a complex role in atherosclerosis progression (Song et al, 2010; Tsuchiya et al, 2012; Z. Z. Zhang, Chen, et al, 2021). Song et al (2010) reported that inhibition of FOXO1 transcriptional activity is responsible for reduced lipid accumulation in macrophages after metformin treatment.…”

Section: Discussionmentioning

confidence: 99%

“…Since FOXO1 mediates the transcription of distinct genes, it exerts various biological effects (Song et al, 2010; Z. Z. Zhang, Chen, et al, 2021). Z.…”

Section: Discussionmentioning

confidence: 99%

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Long noncoding RNA THRIL promotes foam cell formation and inflammation in macrophages

Song

Gao

et al. 2022

Cell Biology International

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Tumor necrosis factor-α (TNF-α) and heterogenous nuclear ribonucleoprotein L (hnRNPL)-related immunoregulatory lincRNA (THRIL) is a long noncoding RNA (lncRNA) involved in various inflammatory diseases. However, its role in atherosclerosis is not known. In this study, we aimed to investigate the function of THRIL in mediating macrophage inflammation and foam cell formation. The expression of THRIL was quantified in THP-1 macrophages after treatment with oxidized low-density lipoprotein (oxLDL). The effect of THRIL overexpression and knockdown on oxLDL-induced inflammatory responses and lipid accumulation was determined. THRIL-associated protein partners were identified by RNA pull-down and RNA immunoprecipitation assays.We show that THRIL is upregulated in macrophages after oxLDL treatment. Knockdown of THRIL blocks oxLDL-induced expression of interleukin-1β (IL-1β), IL-6, and TNF-α and lipid accumulation. Conversely, ectopic expression of THRIL enhances inflammatory gene expression and lipid deposition in oxLDL-treated macrophages. Moreover, THRIL depletion increases cholesterol efflux from macrophages and the expression of ATPbinding cassette transporter (ABC) A1 and ABCG1. FOXO1 is identified as a protein partner of THRIL and promotes macrophage inflammation and lipid accumulation. Furthermore, overexpression of FOXO1 restores lipid accumulation and inflammatory cytokine production in THRIL-depleted macrophages. In conclusion, our data suggest a model where THRIL interacts with FOXO1 to promote macrophage inflammation and foam cell formation. THRIL may represent a therapeutic target for atherosclerosis.

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“…[74][75][76] More recently, we found that CTRP1 inhibits cholesterol efflux to apolipoprotein A-I and promotes foam cell formation in THP-1 macrophages. 77 Mechanistically, CTRP1 decreases miR-424-5p levels, which in turn enhances forkhead box O1 content in the nucleus and downregulates ABCA1 expression. 77 It is not clear, however, whether CTRP1 can regulate ABCG1 expression.…”

Section: Ctrp1 Promotes Macrophage Foam Cell Formationmentioning

confidence: 99%

C1q Tumor Necrosis Factor–Related Protein 1: A Promising Therapeutic Target for Atherosclerosis

Zhang

Wang

Yin

2022

Journal of Cardiovascular Pharmacology

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:Atherosclerosis serves as the pathological basis of most cardiovascular and cerebrovascular diseases. C1q tumor necrosis factor–related protein 1 (CTRP1) is a 35-kDa glycoprotein synthesized by various tissues and cells, such as adipose tissue and macrophages. As an adiponectin paralog, CTRP1 signals through adiponectin receptor 1 and participates in a variety of pathophysiological processes. Circulating CTRP1 levels are significantly increased in patients with coronary artery disease. Importantly, CTRP1 was shown to accelerate the development of atherosclerosis by promoting vascular inflammation, macrophage foam cell formation, and endothelial barrier dysfunction. This review focused on recent advances regarding the role of CTRP1 in atherogenesis with an emphasis on its potential as a novel biomarker and a promising therapeutic target for atherosclerosis-related diseases.

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CTRP1 decreases ABCA1 expression and promotes lipid accumulation through the miR‐424‐5p/FoxO1 pathway in THP‐1 macrophage‐derived foam cells

Cited by 8 publications

References 36 publications

Knockdown of mesenchymal stem cell‑derived exosomal LOC100129516 suppresses the symptoms of atherosclerosis via upregulation of the PPARγ/LXRα/ABCA1 signaling pathway

Knockdown of mesenchymal stem cell‑derived exosomal LOC100129516 suppresses the symptoms of atherosclerosis via upregulation of the PPARγ/LXRα/ABCA1 signaling pathway

Long noncoding RNA THRIL promotes foam cell formation and inflammation in macrophages

C1q Tumor Necrosis Factor–Related Protein 1: A Promising Therapeutic Target for Atherosclerosis

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