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

Abstract

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.

High-Density Lipoproteins: A Role in Inflammation in COPD

“…These changes intensified with age and were accompanied by disruption of alveolar architecture and epithelialization of the remaining alveoli as a result of hyperplasia of type II pneumocytes [ 174 ]. These studies showed decreased expression of ABCA1 in lung tissues in smoking and COPD patients [ 175 ].…”

“…Importantly, smoking impairs reverse cholesterol transport mediated by ABCA1 and ABCG1 [ 175 , 204 , 205 ]. This may lead to an increase in the number of macrophages overloaded with cholesterol, which contributes to their inflammatory activation [ 36 , 136 ].…”

Clinical Significance of Lipid Transport Function of ABC Transporters in the Innate Immune System

“…Thus, members of the ABCA subfamily play a significant role in the mechanisms of innate immunity mediated by lipid transport, which is of great clinical importance [78,79].…”

Anti-Inflammatory Function of Fatty Acids and Involvement of Their Metabolites in the Resolution of Inflammation in Chronic Obstructive Pulmonary Disease

“…Studies in recent years have convincingly demonstrated the involvement of lipids in inflammation. Smoking has been shown to disrupt the normal processes that maintain lipid homeostasis in the lungs, which may be part of the pathogenesis of COPD [ 7 ]. It should be noted that cigarette smoke contributes to an oxidant/antioxidant imbalance due to exogenous reactive oxygen species (ROS).…”