About this item:

33 Views | 19 Downloads

Author Notes:

Correspondence: Xinling Du xinlingdu@hust.edu.cn

Author contributions: CZ, XD, ZL, and ND conceived and designed the study. RL, CZ, and FX performed the experiments, analyzed the data and wrote the manuscript. XZ, XH, and JS contributed to the discussion of the study and the manuscript. All authors read and approved the manuscript.

Acknowledgements: We thank LetPub (www.letpub.com) for its linguistic assistance during the preparation of this manuscript.

Disclosures: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.


Research Funding:

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].


  • Science & Technology
  • Life Sciences & Biomedicine
  • Cardiac & Cardiovascular Systems
  • Cardiovascular System & Cardiology
  • PP2A (protein phosphatase 2A)
  • atherosclerosis
  • foam cell formation
  • p38
  • CD36
  • Low-density lipoprotein cholesterol
  • Expression
  • Dysfunction
  • Inhibition
  • Induction
  • Migration
  • Promotes
  • Target
  • PCSK9
  • PP2A

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

Journal Title:

Frontiers in Cardiovascular Medicine


Volume 8


, Pages 745009-745009

Type of Work:

Article | Final Publisher PDF


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.

Copyright information:

© 2022 Li, Zhang, Xie, Zhou, Hu, Shi, Du, Lin and Dong.

This is an Open Access work distributed under the terms of the Creative Commons Attribution 4.0 International License (https://creativecommons.org/licenses/by/4.0/rdf).
Export to EndNote