Publication

Protein Phosphatase 2A Deficiency in Macrophages Increases Foam Cell Formation and Accelerates Atherosclerotic Lesion Development

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Last modified
  • 05/20/2025
Type of Material
Authors
    Rui Li, Huazhong University of Science & TechnologyChao Zhang, Huazhong University of Science & TechnologyFei Xie, Huazhong University of Science & TechnologyXianming Zhao, Huazhong University of Science and TechnologyXingjian Hu, Huazhong University of Science & TechnologyJiawei Shi, Huazhong University of Science & TechnologyXinling Du, Huazhong University of Science & TechnologyZhiyong Lin, Emory UniversityNianguo Dong, Huazhong University of Science & Technology
Language
  • English
Date
  • 2022-01-18
Publisher
  • Frontiers Media S.A.
Publication Version
Copyright Statement
  • © 2022 Li, Zhang, Xie, Zhou, Hu, Shi, Du, Lin and Dong.
License
Final Published Version (URL)
Title of Journal or Parent Work
Volume
  • 8
Start Page
  • 745009
End Page
  • 745009
Grant/Funding Information
  • This work was financially supported by the grant from the National Natural Science Foundation of China [81600354 to CZ] and part of the grant from the National Key R and D Program of China [2016YFA0101100 to ND].
Supplemental Material (URL)
Abstract
  • Protein phosphatase 2A (PP2A), a crucial serine/threonine phosphatase, has recently been reported to play an important role in cardiovascular disease. Previous studies have hinted that PP2A is involved in atherosclerosis formation, but the associated mechanisms remain poorly understood. In this study, we investigate the role of PP2A in the pathogenesis of atherosclerosis. In human atherosclerotic coronary arteries, we found that the expression and activity of PP2A decreased significantly when compared to non-atherosclerotic arteries. Additional experiments demonstrated that pharmacological inhibition of PP2A aggravated atherosclerosis of ApoE-/- mice. Considering the central role of macrophages in atherosclerosis, mice with conditional knockout of the PP2A-Cα subunit in myeloid cells were produced to investigate the function of PP2A in macrophages. Results showed that PP2A deficiency in myeloid cells aggravated atherosclerotic lesions in mice. in vitro experiments indicated that PP2A-deficient macrophages had an enhanced ability of lipid uptake and foam cell formation. Mechanistically, the deficiency of the PP2A in macrophages led to an increase in the phosphorylation level of p38, which contributed to the elevated expression of scavenger receptor CD36, a key factor involved in lipoprotein uptake. Our data suggest that PP2A participates in the pathophysiological process of atherosclerosis. The decrease of PP2A expression and activity in macrophages is a crucial determinant for foam cell formation and the initiation of atherosclerosis. Our study may provide a potential novel approach for the treatment of atherosclerosis.
Author Notes
Keywords
Research Categories
  • Health Sciences, Medicine and Surgery
  • Biology, Cell
  • Biology, Microbiology

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