Regulation of ATP binding cassette transporter A1 (ABCA1) expression: cholesterol-dependent and - independent signaling pathways with relevance to inflammatory lung disease

• Published in: Respiratory research Vol. 21; no. 1; p. 250
• Main Authors: He, Patrick, Gelissen, Ingrid C, Ammit, Alaina J
• Format: Journal Article
• Language: English
• Published: England BioMed Central Ltd 25.09.2020; BioMed Central; BMC
• Subjects: ABCA1; ABCA1 protein; Adenosine triphosphate; Animals; Arteriosclerosis; Asthma; Asthma - genetics; Asthma - metabolism; Atherosclerosis; ATP; ATP Binding Cassette Transporter 1 - biosynthesis; ATP Binding Cassette Transporter 1 - genetics; ATP-binding protein; Bile; Binding; Blood cholesterol; Cardiovascular diseases; Carrier proteins; Cellular signal transduction; Chlamydia; Cholesterol; Cholesterol - genetics; Cholesterol - metabolism; Chronic conditions; Chronic illnesses; Chronic obstructive pulmonary disease; Cigarette smoke; COPD; Cytokines; Development and progression; Gene Expression; Genotype & phenotype; Health aspects; Homeostasis; Humans; Inflammation; Inflammation Mediators - metabolism; Investigations; Lipids; Liver; Low density lipoprotein; Lung diseases; Lung Diseases - genetics; Lung Diseases - metabolism; Lung diseases, Obstructive; Lungs; Obstructive lung disease; Pathogenesis; Proteins; Pulmonary Disease, Chronic Obstructive - genetics; Pulmonary Disease, Chronic Obstructive - metabolism; Review; Signal transduction; Signal Transduction - physiology; Signaling; Surfactants; Therapeutic applications; TNF; Australia; ABCA1; Inflammation; TNF; Cholesterol; Cigarette smoke; COPD
• ISSN: 1465-993X; 1465-9921; 1465-993X; 1465-9921
• DOI: 10.1186/s12931-020-01515-9

The role of the ATP binding cassette transporter A1 (ABCA1) in maintaining cellular lipid homeostasis in cardiovascular disease is well established. More recently, the important beneficial role played by ABCA1 in modulating pathogenic disease mechanisms, such as inflammation, in a broad range of chronic conditions has been realised. These studies position ABCA1 as a potential therapeutic target in a diverse range of diseases where inflammation is an underlying cause. Chronic respiratory conditions such as asthma and chronic obstructive pulmonary disease (COPD) are driven by inflammation, and as such, there is now a growing recognition that we need a greater understanding of the signaling pathways responsible for regulation of ABCA1 expression in this clinical context. While the signaling pathways responsible for cholesterol-mediated ABCA1 expression have been clearly delineated through decades of studies in the atherosclerosis field, and thus far appear to be translatable to the respiratory field, less is known about the cholesterol-independent signaling pathways that can modulate ABCA1 expression in inflammatory lung disease. This review will identify the various signaling pathways and ligands that are associated with the regulation of ABCA1 expression and may be exploited in future as therapeutic targets in the setting of chronic inflammatory lung diseases.