MafB promotes atherosclerosis by inhibiting foam-cell apoptosis
Open accessAbstract
MafB is a transcription factor that induces myelomonocytic differentiation. However, the precise role of MafB in the pathogenic function of macrophages has never been clarified. Here we demonstrate that MafB promotes hyperlipidemic atherosclerosis by suppressing foam-cell apoptosis. Our data show that MafB is predominantly expressed in foam cells found within atherosclerotic lesions, where MafB mediates the oxidized LDL-activated LXR/RXR-induced expression of apoptosis inhibitor of macrophages (AIM). In the absence of MafB, activated LXR/RXR fails to induce the expression of AIM, a protein that is normally responsible for protecting macrophages from apoptosis; thus, Mafb-deficient macrophages are prone to apoptosis. Haematopoietic reconstitution with Mafb-deficient fetal liver cells in recipient LDL receptor-deficient hyperlipidemic mice revealed accelerated foam-cell apoptosis, which subsequently led to the attenuation of the early atherogenic lesion. These findings represent the first evidence that the macrophage-affiliated MafB transcription factor participates in the acceleration of atherogenesis.
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In early atherogenesis, hyperlipidaemic mouse observations support that efficient efferocytosis of apoptotic foam cells reduces atherosclerotic lesion development.
“In early atherogenesis, observations in hyperlipidaemic mice support the idea that efficient efferocytosis of apoptotic foam cells reduces the development of atherosclerotic lesions176.”
From Inflammation and its resolution in atherosclerosis: mediators and therapeutic opportunities (2019) · cites this paper as [176]
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- Authors
- Hamada, M., Nakamura, M., Tran, M. T. N., Moriguchi, T., Hong, C., Ohsumi, T., Dinh, T. T. H., Kusakabe, M., Hattori, M., Katsumata, T., Arai, S., Nakashima, K., Kudo, T., Kuroda, E., Wu, C.-H., Kao, P.-H., Sakai, M., Shimano, H., Miyazaki, T., Tontonoz, P., & Takahashi, S.
- Affiliations
- University of Tsukuba (JP)
- Tohoku University (JP)
- Howard Hughes Medical Institute (US)
- Center for Disease Biology and Integrative Medicine, The University of Tokyo (JP)
- Immunology Frontier Research Center, The University of Osaka (JP)
- National Taiwan University (TW)
- Chang Gung Memorial Hospital (TW)
- Hokkaido University (JP)
- Corresponding author
- Hamada, Michito
- Takahashi, Satoru
- ORCID
- Venue
- Nature Communications
- Published
- 2014-01-20
- Volume
- 5
- Issue
- 1
- Pages
- 3147-3147
- ISSN
- 2041-1723 (ISSN-L)
- OpenAlex
- W2025696553
- Cited by
- 111
- References
- 48
- Citations by year
- 2026: 6 · 2025: 7 · 2024: 6 · 2023: 8 · 2022: 11 · 2021: 16 · 2020: 5 · 2019: 13 · 2018: 10 · 2017: 7 · 2016: 8 · 2015: 10 · 2014: 4
- FWCI
- 4.42
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Nature Communications (publishedVersion)
- PubMed (publishedVersion)
- RePEc: Research Papers in Economics (submittedVersion)
- Funders
- Takeda Science Foundation (25860205, 23118504)
- Uehara Memorial Foundation (25860205, 23118504)
- Ministry of Education, Culture, Sports, Science and Technology (25860205, 23118504)
- University of Tsukuba
- Japan Society for the Promotion of Science (24650228, 21220009, 25461494, 24590371)
- Topics
- Life Sciences › Immunology and Microbiology › Immunology › Atherosclerosis and Cardiovascular Diseases
- Health Sciences › Medicine › Surgery › Cholesterol and Lipid Metabolism
- Health Sciences › Medicine › Surgery › Lipoproteins and Cardiovascular Health
- Keywords
- MAFB, atherosclerosis, foam cells, macrophage apoptosis, apoptosis inhibitor of macrophage, oxidized LDL, hyperlipidemia, transcription factors, atherogenesis, macrophage differentiation
- MeSH terms
- Liver X Receptors, Animals, Base Sequence, Foam Cells, Humans, Mice, Inbred C57BL, Mice, Transgenic, Molecular Sequence Data, Receptors, Immunologic, Sequence Homology, Nucleic Acid, Apoptosis, Retinoid X Receptors, Atherosclerosis, Apoptosis Regulatory Proteins, Receptors, Scavenger, MafB Transcription Factor, Mice, Orphan Nuclear Receptors
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