DOI: 10.1002/ame2.12266
Overexpressed PKM2 promotes macrophage phagocytosis and atherosclerosis
Xiaochen Gai1
Fangming Liu1
Yuting Wu1
Baohui Zhang2
Bufu Tang3
Kezhuo Shang1
Lianmei Wang4
Haihong Zhang1
Yixin Chen5
Shuhui Yang1
Weiwei Deng1
Peng Li6
Jing Wang7
Hongbing Zhang1
1.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,China2.Department of Physiology,School of Life Science,China Medical University,Shenyang,China3.Department of Radiology,Sir Run Run Shaw Hospital,Zhejiang University School of Medicine,Hangzhou,China4.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;Institute of Chinese Materia Medica,China Academy of Chinese Medical Sciences,Beijing,China5.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,China6.School of Life Sciences,Westlake University,Hangzhou,China7.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
摘要：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-/-back-ground(ApoE-/-,PKM2KI/KI and Lyz2-cre,ApoE-/-,and PKM2flox/fox)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 mac-rophage 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.
机标关键词：atherosclerosismacrophageoverexpressedphagocytosispromotes
论文发表日期：2023-04-28
在线出版日期：2025-08-15（本平台首次上网日期，不代表文献的发表时间）
页数：11( 92-102 )
英文信息