Article ; Online: ABCA1 and ABCG1 as potential therapeutic targets for the prevention of atherosclerosis.
Journal of pharmacological sciences
2021 Volume 148, Issue 2, Page(s) 197–203
Abstract: Prevention of atherosclerosis is important because it is a risk factor for cardiovascular diseases globally. One of the causes of atherosclerosis is accumulation of cholesterol and triglycerides in peripheral cells. ATP-binding cassette protein A1 (ABCA1) ...
| Abstract | Prevention of atherosclerosis is important because it is a risk factor for cardiovascular diseases globally. One of the causes of atherosclerosis is accumulation of cholesterol and triglycerides in peripheral cells. ATP-binding cassette protein A1 (ABCA1) and G1 (ABCG1) are important in eliminating excess cholesterol from cells including macrophages and forming high-density lipoprotein, which contributes to the prevention and regression of atherosclerosis. Enhanced cholesterol efflux activities of ABCA1 and ABCG1 are expected to prevent the progression of atherosclerosis. ABCA1 and ABCG1 are induced by the LXR/RXR pathway and regulated transcriptionally, post-transcriptionally, and post-translationally. Their mRNAs are destabilized by microRNAs and their cellular localization and degradation are regulated by other proteins and phosphorylation. Furthermore, ABCA1 and ABCG1 suppress the inflammatory responses of macrophages. These proteins are effective targets because their increased activities can suppress cholesterol accumulation and inflammation in macrophages. Moreover, ABCA1 and ABCG1 prevent amyloid β accumulation; therefore, their increased activity may prevent Alzheimer's disease. Because ABCA1 and ABCG1 are affected by transcriptional, post-transcriptional, and post-translational regulation, the regulatory factors involved could also serve as therapeutic targets. This review highlights that ABCA1 and ABCG1 could be potential therapeutic targets for preventing atherosclerosis by regulating their expression, degradation, and localization. |
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| MeSH term(s) | ATP Binding Cassette Transporter 1/genetics ; ATP Binding Cassette Transporter 1/metabolism ; ATP Binding Cassette Transporter 1/physiology ; ATP Binding Cassette Transporter, Subfamily G, Member 1/genetics ; ATP Binding Cassette Transporter, Subfamily G, Member 1/metabolism ; ATP Binding Cassette Transporter, Subfamily G, Member 1/physiology ; Alzheimer Disease/prevention & control ; Amyloid beta-Peptides/metabolism ; Atherosclerosis/etiology ; Atherosclerosis/genetics ; Atherosclerosis/metabolism ; Atherosclerosis/prevention & control ; Biological Transport/genetics ; Cholesterol/metabolism ; Disease Progression ; Humans ; Macrophages/metabolism ; Molecular Targeted Therapy ; Retinoid X Receptors/metabolism ; Signal Transduction/genetics ; Signal Transduction/physiology ; Transcription, Genetic/physiology ; Triglycerides/metabolism |
| Chemical Substances | ABCA1 protein, human ; ABCG1 protein, human ; ATP Binding Cassette Transporter 1 ; ATP Binding Cassette Transporter, Subfamily G, Member 1 ; Amyloid beta-Peptides ; Retinoid X Receptors ; Triglycerides ; Cholesterol (97C5T2UQ7J) |
| Language | English |
| Publishing date | 2021-12-01 |
| Publishing country | Japan |
| Document type | Journal Article ; Review |
| ZDB-ID | 2104264-0 |
| ISSN | 1347-8648 ; 1347-8613 |
| ISSN (online) | 1347-8648 |
| ISSN | 1347-8613 |
| DOI | 10.1016/j.jphs.2021.11.005 |
| Database | MEDical Literature Analysis and Retrieval System OnLINE |
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