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Overexpressed PKM2 promotes macrophage phagocytosis and atherosclerosis

Xiaochen Gai1, Fangming Liu1, Yuting Wu1

  • 1State Key Laboratory of Medical Molecular Biology, Department of Physiology, Institute of Basic Medical Sciences and School of Basic Medicine, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.

Animal Models and Experimental Medicine
|August 17, 2022
PubMed
Abstract

Insights

Pyruvate kinase muscle 2 (PKM2) fuels macrophage activity and atherosclerosis. Inhibiting PKM2 offers a potential therapeutic strategy for treating this cardiovascular disease.

Area of Science:

  • Biochemistry
  • Immunology
  • Cardiovascular Research

Background:

  • Pyruvate kinase muscle 2 (PKM2) expression is elevated in macrophages of patients with atherosclerotic coronary artery disease.
  • The specific role of PKM2 in the development of atherosclerosis remains to be elucidated.

Purpose of the Study:

  • To investigate the functional role of PKM2 in macrophage phagocytosis and its contribution to atherosclerosis.
  • To evaluate the therapeutic potential of targeting PKM2 in a mouse model of atherosclerosis.

Main Methods:

  • Generated global and myeloid cell-specific PKM2 knock-in mice on an ApoE-/- background.
  • Assessed macrophage phagocytosis in wild-type and PKM2 knock-in macrophages.
  • Administered the PKM2 inhibitor shikonin (SKN) to atherosclerotic mice.

Main Results:

  • Oxidized low-density lipoprotein (oxLDL) increased PKM2 expression in macrophages, which in turn enhanced oxLDL uptake.
  • Overexpression of PKM2 accelerated atherosclerosis progression in mice.
  • Shikonin treatment effectively inhibited the progression of atherosclerosis in mice.

Conclusions:

  • PKM2 plays a critical role in promoting macrophage phagocytosis and accelerating atherosclerosis.
  • Targeting PKM2 represents a promising therapeutic avenue for managing atherosclerosis.
Keywords:
atherosclerosislow-density lipoproteinmacrophagepyruvate kinase muscle 2

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