Overexpressed PKM2 promotes macrophage phagocytosis and atherosclerosis

被引：0
|
作者：
Xiaochen Gai [1 ]
Fangming Liu [1 ]
Yuting Wu [1 ]
Baohui Zhang [2 ]
Bufu Tang [3 ]
Kezhuo Shang [1 ]
Lianmei Wang [1 ,4 ]
Haihong Zhang [1 ]
Yixin Chen [5 ]
Shuhui Yang [1 ]
Weiwei Deng [1 ]
Peng Li [6 ]
Jing Wang [7 ]
Hongbing Zhang [1 ]
机构：
[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
[2] Department of Physiology,School of Life Science,China Medical University
[3] Department of Radiology,Sir Run Run Shaw Hospital,Zhejiang University School of Medicine
[4] Institute of Chinese Materia Medica,China Academy of Chinese Medical Sciences
[5] 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
[6] School of Life Sciences,Westlake University
[7] 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
来源：
Animal Models and Experimental Medicine | 2023年 / 6卷 / 02期
基金：
国家重点研发计划; 中国国家自然科学基金;
关键词：
D O I：
暂无
中图分类号：
R54 [心脏、血管（循环系）疾病];
学科分类号：
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-/-background(ApoE-/-,PKM2KI/KIand 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 PKM2accelerated 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.
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页码：92 / 102
页数：11
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