Overexpressed PKM2 promotes macrophage phagocytosis and atherosclerosis

Xiaochen Gai; Fangming Liu; Yuting Wu; Baohui Zhang; Bufu Tang; Kezhuo Shang; Lianmei Wang; Haihong Zhang; Yixin Chen; Shuhui Yang; Weiwei Deng; Peng Li; Jing Wang; Hongbing Zhang

doi:10.1002/ame2.12266

Animal Models and Experimental Medicine (Apr 2023)

Overexpressed PKM2 promotes macrophage phagocytosis and atherosclerosis

Xiaochen Gai,
Fangming Liu,
Yuting Wu,
Baohui Zhang,
Bufu Tang,
Kezhuo Shang,
Lianmei Wang,
Haihong Zhang,
Yixin Chen,
Shuhui Yang,
Weiwei Deng,
Peng Li,
Jing Wang,
Hongbing Zhang

Affiliations

Xiaochen Gai: State 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
Fangming Liu: State 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
Yuting Wu: State 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
Baohui Zhang: Department of Physiology, School of Life Science China Medical University Shenyang China
Bufu Tang: Department of Radiology Sir Run Run Shaw Hospital, Zhejiang University School of Medicine Hangzhou China
Kezhuo Shang: State 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
Lianmei Wang: State 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
Haihong Zhang: State 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
Yixin Chen: Department of Cardiac Surgery, Fuwai Hospital, Stata Key Laboratory of Cardiovascular Disease, National Center for Cardiovascular Diseases of China Chinese Academy of Medical Sciences and Peking Union Medical College Beijing China
Shuhui Yang: State 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
Weiwei Deng: State 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
Peng Li: School of Life Sciences Westlake University Hangzhou China
Jing Wang: State Key Laboratory of Medical Molecular Biology, Department of Pathophysiology, Institute of Basic Medical Sciences and School of Basic Medicine Chinese Academy of Medical Sciences and Peking Union Medical College Beijing China
Hongbing Zhang: State 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

DOI: https://doi.org/10.1002/ame2.12266
Journal volume & issue: Vol. 6, no. 2
pp. 92 – 102

Abstract

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Abstract Background The expression of pyruvate kinase muscle 2 (PKM2) is augmented in macrophages of patients with atherosclerotic coronary artery disease. The role of PKM2 in atherosclerosis is to be determined. Methods Global and myeloid cell‐specific PKM2 knock‐in mice with ApoE−/− background (ApoE−/−, PKM2KI/KI and Lyz2‐cre, ApoE−/−, and PKM2flox/flox) were produced to evaluate the clinical significance of PKM2 in atherosclerosis development. Wild‐type and PKM2 knock‐in macrophages were isolated to assess the function of PKM2 in macrophage phagocytosis. Atherosclerotic mice were treated with PKM2 inhibitor shikonin (SKN) to evaluate the therapeutic potential of PKM2 suppression in atherosclerosis. Results Oxidized low‐density lipoprotein (oxLDL) upregulated PKM2 in macrophages. PKM2 in return promoted the uptake of oxLDL by macrophages. Overexpressed PKM2 accelerated atherosclerosis in mice. SKN blocked the progress of mouse atherosclerosis. Conclusions PKM2 accelerates macrophage phagocytosis and atherosclerosis. Targeting PKM2 is a potential therapy for atherosclerosis.

Published in Animal Models and Experimental Medicine

ISSN: 2576-2095 (Online)
Publisher: Wiley
Country of publisher: Australia
LCC subjects: Medicine: Medicine (General)
Website: https://onlinelibrary.wiley.com/journal/25762095

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