Participation of ABCA1 Transporter in Pathogenesis of Chronic Obstructive Pulmonary Disease

Kotlyarov, Stanislav

doi:10.3390/ijms22073334

Cited by 17 publications

(15 citation statements)

References 229 publications

(315 reference statements)

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“…Literature data suggest that smoking has a significant effect on the expression and function of ABCA1 in the respiratory tract. The data obtained in recent years have expanded our understanding of the function of the ABCA1 protein [ 30 ]. This representative of a large family of ABC transporters is a key participant in the formation of high-density lipoprotein (HDL) due to its ability to export cholesterol and phospholipids from the cell to the extracellular acceptor.…”

Section: Discussionmentioning

confidence: 99%

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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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Section: Discussionmentioning

confidence: 99%

“…Changing the cholesterol content in macrophages participates in the regulation of inflammation, phagocytosis, and apoptosis. ABCA1 is expressed at high levels in lung tissues and as it is believed it plays an important role in the development of COPD [ 29 , 30 ]. Lipid metabolism plays an important role in lung function.…”

Section: Introductionmentioning

confidence: 99%

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

Kotlyarov

Kotlyarova

2021

Membranes

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“…ABCA1 ensures the export of cholesterol from macrophages. This function is considered one of the key ones in ensuring cholesterol homeostasis [21,22]. Decreased functional activity of ABCA1 leads to cellular accumulation of cholesterol with the formation of "foam cells".…”

Section: Discussionmentioning

confidence: 99%

Analysis of ABC Transporter Gene Expression in Atherosclerosis

Kotlyarov

Kotlyarova

2021

Cardiogenetics

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ABC transporters are a large family of membrane proteins that transport chemically diverse substrates across the cell membrane. Disruption of transport mechanisms mediated by ABC transporters causes the development of various diseases, including atherosclerosis. Methods: A bioinformatic analysis of a dataset from Gene Expression Omnibus (GEO) was performed. A GEO dataset containing data on gene expression levels in samples of atherosclerotic lesions and control arteries without atherosclerotic lesions from carotid, femoral, and infrapopliteal arteries was used for analysis. To evaluate differentially expressed genes, a 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 obtained data indicate the differential expression of many ABC transporters belonging to different subfamilies. The differential expressions of ABC transporter genes involved in lipid transport, mechanisms of multidrug resistance, and mechanisms of ion exchange are shown. Differences in the expression of transporters in tissue samples from different arteries are established. Conclusions: The expression of ABC transporter genes demonstrates differences in atherosclerotic samples and normal arteries, which may indicate the involvement of transporters in the pathogenesis of atherosclerosis.

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“…Moreover, IL-6 was reported to induce the ABCA1 expression and to enhance the transporter-mediated cholesterol efflux to apoA-I with the participation of the JAK2/STAT3 pathway [ 139 ]. Thus IL-6 production by lipid-loaded macrophages promotes ABCA1 gene expression, which leads to increased ABCA1-mediated cholesterol efflux via JAK2/STAT3 activation, thereby reducing foam cell formation and free cholesterol accumulation [ 142 ]. Apart from IL-6, other cytokines can also modulate ABCA1 expression, including interferon γ (IFN-γ), platelet-derived growth factor and IL-1β, which have an inhibitory effect, whereas IL-10 and transforming growth factor-beta 1 have an inducing effect [ 131 ].…”

Section: Immunomodulatory Functions Of Hdlmentioning

confidence: 99%

Current Understanding of the Immunomodulatory Activities of High-Density Lipoproteins

Trakaki

Marsche

2021

Biomedicines

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Lipoproteins interact with immune cells, macrophages and endothelial cells - key players of the innate and adaptive immune system. High-density lipoprotein (HDL) particles seem to have evolved as part of the innate immune system since certain HDL subspecies contain combinations of apolipoproteins with immune regulatory functions. HDL is enriched in anti-inflammatory lipids, such as sphingosine-1-phosphate and certain saturated lysophospholipids. HDL reduces inflammation and protects against infection by modulating immune cell function, vasodilation and endothelial barrier function. HDL suppresses immune cell activation at least in part by modulating the cholesterol content in cholesterol/sphingolipid-rich membrane domains (lipid rafts), which play a critical role in the compartmentalization of signaling pathways. Acute infections, inflammation or autoimmune diseases lower HDL cholesterol levels and significantly alter HDL metabolism, composition and function. Such alterations could have a major impact on disease progression and may affect the risk for infections and cardiovascular disease. This review article aims to provide a comprehensive overview of the immune cell modulatory activities of HDL. We focus on newly discovered activities of HDL-associated apolipoproteins, enzymes, lipids, and HDL mimetic peptides.

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Participation of ABCA1 Transporter in Pathogenesis of Chronic Obstructive Pulmonary Disease

Cited by 17 publications

References 229 publications

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

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

Analysis of ABC Transporter Gene Expression in Atherosclerosis

Current Understanding of the Immunomodulatory Activities of High-Density Lipoproteins

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