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A novel therapeutic strategy for atherosclerosis: autophagy-dependent cholesterol efflux

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Abstract

Atherosclerosis (AS) is a chronic inflammatory disease characterized by abnormal lipid metabolism. Foam cell formation is also known as an early event of AS. Cholesterol efflux is a process whereby cholesterol is excreted from foam cells through transporters, which serves as one of the effective regulatory mechanisms to prevent AS. Autophagy is a biodegradable mechanism, and lipophagy is a special form of autophagy that selectively degrades lipids. Cholesterol efflux is regulated by several mechanisms. Moreover, numerous studies have shown that autophagy is also process whereby cholesterol efflux is regulated. In early studies, scholars found that cholesterol efflux is related to autophagy. Subsequent studies have shown that various targeted molecules can induce autophagy and promote the expression of cholesterol transporters (such as LXRα, ABCA1, and ABCG1) through specific signaling pathways. Several novel treatments for AS use these small molecules as entry points for research and development based on autophagy. However, this autophagy-dependent cholesterol efflux involves many different molecular mechanisms. This not only indicates that cholesterol efflux is the result of multiple factors, but also that autophagy, which mediates cholesterol efflux, is a complex physiological mechanism. Through a literature review, we found that the role of autophagy in cholesterol efflux is related to cell type and is regulated by both the level of autophagy and the mechanism that triggers autophagy. In this review, we aim to discuss the role of autophagy in cholesterol efflux from many aspects based on recent relevant studies to aid in the treatment of AS.

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Acknowledgements

The authors would like to thank Editage for technical editing of the manuscript.

Funding

This research was supported by the Nature Science Foundation of Heilongjiang Province (No. LH2020H137).

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Authors and Affiliations

  1. Department of Laboratory Medicine, The First Hospital of Qiqihar, Qiqihar, 161005, China

    Haipeng Guo, Chao Zhang, Song Jiang, Weijia Wang, Hongzhe Hu & Xiaofei Liang

  2. Department of Laboratory Medicine, Affiliated Qiqihar Hospital, Southern Medical University, Qiqihar, 161005, China

    Haipeng Guo, Chao Zhang, Song Jiang, Weijia Wang, Hongzhe Hu & Xiaofei Liang

  3. Department of Traditional Chinese Geriatric Medicine, The First Hospital of Qiqihar, Qiqihar, 161005, China

    Dongmei Wei

  4. Department of Traditional Chinese Geriatric Medicine, Affiliated Qiqihar Hospital, Southern Medical University, Qiqihar, 161005, China

    Dongmei Wei

  5. Ministry of Science and Education, The First Hospital of Qiqihar, Qiqihar, 161005, China

    Rui Liu

  6. Ministry of Science and Education, Affiliated Qiqihar Hospital, Southern Medical University, Qiqihar, 161005, China

    Rui Liu

  7. Qiqihar MingZhu Hospital, Qiqihar, 161000, China

    Lijuan Shen

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  1. Haipeng Guo
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  2. Dongmei Wei
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  3. Rui Liu
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  4. Chao Zhang
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  5. Song Jiang
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  7. Hongzhe Hu
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  8. Lijuan Shen
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  9. Xiaofei Liang
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Contributions

Haipeng Guo: conceptualization; Dongmei Wei: writing—original draft; Rui Liu: writing—review and editing; Chao Zhang: drawing and tabulating; Song Jiang: searching literature; Weijia Wang: analyzing literature; Hongzhe Hu: software; Lijuan Shen: project administration; Xiaofei Liang: supervision, funding acquisition. The authors declare that all data were generated in-house and that no paper mill was used.

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Correspondence to Xiaofei Liang.

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Key Points

• Autophagy can regulate cholesterol efflux in foam cells by many molecular mechanisms.

• Autophagy-dependent cholesterol efflux may be related to autophagy level or autophagy mechanism.

• Autophagy-dependent cholesterol efflux is a potential therapeutic strategy for atherosclerosis.

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Guo, H., Wei, D., Liu, R. et al. A novel therapeutic strategy for atherosclerosis: autophagy-dependent cholesterol efflux. J Physiol Biochem 78, 557–572 (2022). https://doi.org/10.1007/s13105-021-00870-5

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  • DOI: https://doi.org/10.1007/s13105-021-00870-5

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