Deficient Chaperone-Mediated Autophagy Promotes Lipid Accumulation in Macrophage
Open accessAbstract
Chaperone-mediated autophagy (CMA) serves as a critical upstream regulator of lipophagy and lipid metabolism in hepatocyte. However, the role of CMA in lipid metabolism of macrophage, the typical component of atherosclerotic plaque, remains unclear. In our study, LAMP-2A (L2A, a CMA marker) was reduced in macrophages exposed to high dose of oleate, and lipophagy was impaired in advanced atherosclerosis in ApoE (-/-) mice. Primary peritoneal macrophages isolated from macrophage-specific L2A-deficient mice exhibited pronounced intracellular lipid accumulation. Lipid regulatory enzymes, including long-chain-fatty-acid-CoA ligase 1 (ACSL1) and lysosomal acid lipase (LAL), were increased and reduced in L2A-KO macrophage, respectively. Other lipid-related proteins, such as SR-A, SR-B (CD36), ABCA1, or PLIN2, were not associated with increased lipid content in L2A-KO macrophage. In conclusion, deficient CMA promotes lipid accumulation in macrophage probably by regulating enzymes involved in lipid metabolism. CMA may represent a novel therapeutic target to alleviate atherosclerosis by promoting lipid metabolism. Graphical abstract.
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Autophagy is known to regulate lipid droplet concentrations.
“a mechanism which is known to regulate LD concentrations27–29”
From APOE4/4 is linked to damaging lipid droplets in Alzheimer’s disease microglia (2024) · cites this paper as [28]
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ApoE-deficient mice develop lesions of all phases of atherosclerosis throughout the arterial tree.
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APOE4/4 is linked to damaging lipid droplets in Alzheimer’s disease microglia
Haney, M. S., Pálovics, R., Munson, C. N., Long, C., Johansson, P. K., Yip, O., Dong, W., Rawat, E., West, E., Schlachetzki, J. C. M., et al. (2024) · Nature · doi:10.1038/s41586-024-07185-7 · Cited by 536 · see citing works
- Authors
- Qiao, L., Wang, H.-F., Xiang, L., Ma, J., Zhu, Q., Xu, D., Zheng, H., Peng, J.-Q., Zhang, S., Lu, H.-X., Chen, W.-Q., & Zhang, Y.
- Affiliations
- Shandong University (CN)
- Corresponding author
- Zhang, Yun
- Venue
- Journal of Cardiovascular Translational Research
- Published
- 2020-04-13
- Volume
- 14
- Issue
- 4
- Pages
- 661-669
- ISSN
- 1937-5387 (ISSN-L)
- 1937-5395
- PMC
- PMC8397667
- OpenAlex
- W3015514397
- Cited by
- 45
- References
- 2
- Citations by year
- 2026: 6 · 2025: 3 · 2024: 7 · 2023: 8 · 2022: 17 · 2021: 1 · 2020: 2
- FWCI
- 5.56
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Locations
- Journal of Cardiovascular Translational Research (publishedVersion, cc-by)
- Europe PMC (PubMed Central) (publishedVersion, other-oa)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Funders
- National Natural Science Foundation of China (81770436)
- National Key Project of Chronic Non-Communicable Diseases of China (2016 YFC1300403)
- Topics
- Health Sciences › Medicine › Epidemiology › Autophagy in Disease and Therapy
- Health Sciences › Medicine › Surgery › Cholesterol and Lipid Metabolism
- Life Sciences › Immunology and Microbiology › Immunology › Atherosclerosis and Cardiovascular Diseases
- Keywords
- chaperone-mediated autophagy, LAMP2A, macrophage lipid accumulation, lipophagy, atherosclerosis, oleate, ApoE-deficient mice, ACSL1, lysosomal acid lipase, lipid metabolism, atherosclerotic plaque
- MeSH terms
- Mice, Knockout, ApoE, Animals, Autophagy, Cells, Cultured, Sterol Esterase, Coenzyme A Ligases, Disease Models, Animal, Male, Mice, Inbred C57BL, Macrophages, Peritoneal, Oleic Acid, Atherosclerosis, Lipid Metabolism, Mice, Lysosomal-Associated Membrane Protein 2
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