ABCA1 and Inflammation

Bi, Xin; Vitali, Cecilia; Cuchel, Marina

doi:10.1161/atvbaha.115.305547

Cited by 23 publications

(11 citation statements)

References 27 publications

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“…The major role of ABCA1 is to remove intracellular excess lipids and to inhibit inflammation (Yin et al, 2010; Bi et al, 2015; Ren et al, 2018). Studies have indicated that ABCA1 expression is decreased in atherosclerotic lesion, and this decrease is associated with the enhanced inflammatory response and atherosclerotic progression (Su et al, 2005; Mukhamedova et al, 2011).…”

Section: Discussionmentioning

confidence: 99%

“…It has been manifested that ATP-binding cassette transporter 1 (ABCA-1) exhibits anti-atherosclerotic roles via promoting cholesterol efflux and inhibiting inflammation (Ogura et al, 2011; Bi et al, 2015; Lake et al, 2017). Chawla et al (2001) reported that ABCA-1 expression is regulated by peroxisome proliferator-activated receptor gamma (PPARγ)-nuclear receptor liver X receptor alpha (LXRα) pathway.…”

Section: Introductionmentioning

confidence: 99%

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Chronic Unpredictable Mild Stress Promotes Atherosclerosis via HMGB1/TLR4-Mediated Downregulation of PPARγ/LXRα/ABCA1 in ApoE-/- Mice

et al. 2019

Front. Physiol.

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Background: Although our previous studies have confirmed that the activation of TLR4 is implicated in the development of atherosclerosis induced by chronic unpredicted mild stress (CUMS), the underling mechanism is largely unclear. Here, we hypothesized that CUMS accelerates atherosclerotic development through lowering PPARγ/LXRα-ABCA1 expression via HMGB1/TLR4 signaling. Methods: In present study, CUMS atherosclerotic animal models were established with AopE -/- mice, and CUMS Raw 264.7 macrophage models were mimicked by high corticosterone treatment, These models were treated with Ethyl pyruvate (EP, an inhibitor of HMGB1), TLR4 inhibitor TAK-242, and PPARγ agonist RSG (Rosiglitazone) to test our hypothesis, respectively. Results: Our results indicated that the protein levels of HMGB1, TLR4, and pro-inflammatory cytokines including IL-1β, TNF-α were elevated with the development of atherosclerosis in CUMS mice, while the expressions of PPARγ, LXRα, and ABCA1 declined. Notably, HMGB1 inhibition by EP reversed CUMS-induced atherosclerotic development, pro-inflammatory cytokines upregulation, and PPARγ/LXRα-ABCA1 downregulation. The same trend was observed in the stressed mice treatment with TAK-242. Further experimental evidences indicated that EP, TAK-242, and RSG treatment notably corrected foam cell formation, HMGB1 release, and down-regulation of LXRα and ABCA1 in CUMS Raw 264.7 macrophage model. Conclusion: These results indicate that CUMS exacerbates atherosclerosis is likely via HMGB1-mediated downregulation of PPARγ/LXRα-ABCA1 through TLR4. These data reveal a novel mechanism by which CUMS aggravates atherosclerosis and may offer a potential therapeutic target for this disease.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Chronic Unpredictable Mild Stress Promotes Atherosclerosis via HMGB1/TLR4-Mediated Downregulation of PPARγ/LXRα/ABCA1 in ApoE-/- Mice

et al. 2019

Front. Physiol.

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“…An important mechanism that ensures the participation of ABCA1 in inflammation is the transporter-mediated regulation of the cholesterol content in the lipid rafts of plasma membranes [ 62 , 63 ]. Lipid rafts are specialized membrane microdomains of the plasma membrane of cells, enriched with cholesterol and sphingolipids.…”

Section: Discussionmentioning

confidence: 99%

Bioinformatic Analysis of ABCA1 Gene Expression in Smoking and Chronic Obstructive Pulmonary Disease

Kotlyarov

Kotlyarova

2021

Membranes

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Smoking is a key modifiable risk factor for developing the chronic obstructive pulmonary disease (COPD). When smoking, many processes, including the reverse transport of cholesterol mediated by the ATP binding cassette transporter A1 (ABCA1) protein are disrupted in the lungs. Changes in the cholesterol content in the lipid rafts of plasma membranes can modulate the function of transmembrane proteins localized in them. It is believed that this mechanism participates in increasing the inflammation in COPD. Methods: Bioinformatic analysis of datasets from Gene Expression Omnibus (GEO) was carried out. Gene expression data from datasets of alveolar macrophages and the epithelium of the respiratory tract in smokers and COPD patients compared with non-smokers were used for the analysis. To evaluate differentially expressed genes, bioinformatic analysis was performed in comparison groups using the limma package in R (v. 4.0.2), and the GEO2R and Phantasus tools (v. 1.11.0). Results: The conducted bioinformatic analysis showed changes in the expression of the ABCA1 gene associated with smoking. In the alveolar macrophages of smokers, the expression levels of ABCA1 were lower than in non-smokers. At the same time, in most of the airway epithelial datasets, gene expression did not show any difference between the groups of smokers and non-smokers. In addition, it was shown that the expression of ABCA1 in the epithelial cells of the trachea and large bronchi is higher than in small bronchi. Conclusions: The conducted bioinformatic analysis showed that smoking can influence the expression of the ABCA1 gene, thereby modulating lipid transport processes in macrophages, which are part of the mechanisms of inflammation development.

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“…The HLA gene complex encodes the human proteins of the major histocompatibility complex (MHC), which is important for presenting processed peptide antigens (Choo, 2007, Neefjes et al, 2011). It is of interest to know whether these changes represent another link between ABCA1 and immune responses, considering the increasingly appreciated relationship between ABCA1 and inflammation, lipid-regulatory effects dependent or not (Bi et al, 2015, Bochem et al, 2015, Tall and Yvan-Charvet, 2015). The HLCs system enables future explorations using unbiased strategies to enhance our understanding of the functions of human hepatic ABCA1.…”

Section: Discussionmentioning

confidence: 99%

ATP-Binding Cassette Transporter A1 Deficiency in Human Induced Pluripotent Stem Cell-Derived Hepatocytes Abrogates HDL Biogenesis and Enhances Triglyceride Secretion

Pashos

Cuchel

et al. 2017

EBioMedicine

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Despite the recognized role of the ATP-binding Cassette Transporter A1 (ABCA1) in high-density lipoprotein (HDL) metabolism, our understanding of ABCA1 deficiency in human hepatocytes is limited. To define the functional effects of human hepatocyte ABCA1 deficiency, we generated induced pluripotent stem cell (iPSC)-derived hepatocyte-like cells (HLCs) from Tangier disease (TD) and matched control subjects. Control HLCs exhibited robust cholesterol efflux to apolipoprotein A-I (apoA-I) and formed nascent HDL particles. ABCA1-deficient HLCs failed to mediate lipid efflux or nascent HDL formation, but had elevated triglyceride (TG) secretion. Global transcriptome analysis revealed significantly increased ANGPTL3 expression in ABCA1-deficient HLCs. Angiopoietin-related protein 3 (ANGPTL3) was enriched in plasma of TD relative to control subjects. These results highlight the required role of ABCA1 in cholesterol efflux and nascent HDL formation by hepatocytes. Furthermore, our results suggest that hepatic ABCA1 deficiency results in increased hepatic TG and ANGPTL3 secretion, potentially underlying the elevated plasma TG levels in TD patients.

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ABCA1 and Inflammation

Cited by 23 publications

References 27 publications

Chronic Unpredictable Mild Stress Promotes Atherosclerosis via HMGB1/TLR4-Mediated Downregulation of PPARγ/LXRα/ABCA1 in ApoE-/- Mice

Chronic Unpredictable Mild Stress Promotes Atherosclerosis via HMGB1/TLR4-Mediated Downregulation of PPARγ/LXRα/ABCA1 in ApoE-/- Mice

Bioinformatic Analysis of ABCA1 Gene Expression in Smoking and Chronic Obstructive Pulmonary Disease

ATP-Binding Cassette Transporter A1 Deficiency in Human Induced Pluripotent Stem Cell-Derived Hepatocytes Abrogates HDL Biogenesis and Enhances Triglyceride Secretion

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