The ABCA1-efferocytosis axis: A new strategy to protect against atherosclerosis
Abstract
Atherosclerosis, a disease process characterized by lipid accumulation and inflammation, is the main cause of coronary heart disease (CHD) and myocardial infarction (MI). Efferocytosis involves the clearance of apoptotic cells by phagocytes. Successful engulfment triggers the release of anti-inflammatory cytokines to suppress atherosclerosis. ABCA1 is a key mediator of cholesterol efflux to apoA-I for the generation of HDL-C in reverse cholesterol transport (RCT). Intriguingly, ABCA1 promotes not only cholesterol efflux but also efferocytosis. ABCA1 promotes efferocytosis by regulating the release of "find-me" ligands, including LPC, and the exposure, release, and expression of "eat-me" ligands, including PtdSer, ANXA1, ANXA5, MEGF10, and GULP1. ABCA1 has a pathway similar to TG2, which is an "eat-me" ligand. ABCA1 has the highest known homology to ABCA7, which controls efferocytosis as the engulfment and processing ligand. In addition, ABCA1 can form several regulatory feedback axes with ANXA1, MEGF10, GULP1, TNFα, and IL-6. Therefore, ABCA1 is the central factor that links cholesterol efflux and apoptotic cell clearance. Several drugs have been studied or approved for apoptotic cell clearance, such as CD47 antibody and PD1-/PD-L1 antibody. In this article, we review the role and mechanism of action of ABCA1 in efferocytosis and focus on new insights into the ABCA1-efferocytosis axis and its potential as a novel therapeutic target in atherosclerosis.
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Apoptotic cells increase ABCA1, which is required for the secretion of find me signals.
“Interestingly, apoptotic cells increase ABCA1, which is required for the secretion of ‘find me’ signals (65, 66).”
From Cholesterol efflux protein, ABCA1, supports anticancer functions of myeloid immune cells (2026) · cites this paper as [66]
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Cholesterol efflux protein, ABCA1, supports anticancer functions of myeloid immune cells
Bendre, S. V., Wang, Y., Hajyousif, B., K C, R., Bhogale, S. G., Pradeep, D., Krawczynska, N., Schane, C. P., Weisser, E., Singh, A., et al. (2026) · Science Advances · doi:10.1126/sciadv.adx5490 · Cited by 8 · see citing works
- Authors
- Chen, W., Li, L., Wang, J., Zhang, R., Zhang, T., Wu, Y., Wang, S., & Xing, D.
- Affiliations
- Qingdao University (CN)
- Corresponding author
- Wu, Yudong
- Wang, Shuai
- Xing, Dongming
- Venue
- Clinica Chimica Acta
- Publisher
- Elsevier BV
- Published
- 2021-07
- Volume
- 518
- Pages
- 1-8
- ISSN
- 0009-8981 (ISSN-L)
- OpenAlex
- W3136719099
- Cited by
- 84
- References
- 6
- Citations by year
- 2026: 13 · 2025: 20 · 2024: 18 · 2023: 21 · 2022: 7 · 2021: 5
- FWCI
- 1.46
- Type
- journal article
- Language
- en
- Open access
- closed
- Licence
- Locations
- Clinica Chimica Acta (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Immunology and Microbiology › Immunology › Phagocytosis and Immune Regulation
- Health Sciences › Medicine › Surgery › Cholesterol and Lipid Metabolism
- Life Sciences › Immunology and Microbiology › Immunology › Atherosclerosis and Cardiovascular Diseases
- Keywords
- ABCA1, efferocytosis, atherosclerosis, cholesterol efflux, reverse cholesterol transport, HDL cholesterol, phosphatidylserine, annexin A1, MEGF10, tissue transglutaminase, ABCA7, anti-inflammatory cytokines, therapeutic target
- MeSH terms
- Cholesterol, Humans, Inflammation, Phagocytosis, ATP-Binding Cassette Transporters, Adaptor Proteins, Signal Transducing, Atherosclerosis, ATP Binding Cassette Transporter 1
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