Overexpressed PKM2 promotes macrophage phagocytosis and atherosclerosis.
Overexpressed PKM2 promotes macrophage phagocytosis and atherosclerosis.
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过表达的PKM2促进巨噬细胞吞噬作用和动脉粥样硬化
DOI：
10.1002/ame2.12266
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发表时间：
2023-04
影响因子：
3.7
通讯作者：
Zhang, Hongbing
中科院分区：
文献类型：
--
作者：
Gai, Xiaochen;Liu, Fangming;Wu, Yuting;Zhang, Baohui;Tang, Bufu;Shang, Kezhuo;Wang, Lianmei;Zhang, Haihong;Chen, Yixin;Yang, Shuhui;Deng, Weiwei;Li, Peng;Wang, Jing;Zhang, Hongbing
冠状动脉粥样硬化性疾病患者巨噬细胞中丙酮酸激酶肌2 （PKM2）的表达增加。PKM2在动脉粥样硬化中的作用有待确定。产生具有ApoE−/−背景（ApoE−/−，PKM2 KI/KI和Lyz2‐cre， ApoE−/−和PKM2 flox/flox）的全球和髓细胞特异性PKM2敲入小鼠，以评估PKM2在动脉粥样硬化发展中的临床意义。分离野生型和PKM2敲入巨噬细胞，以评估PKM2在巨噬细胞吞噬中的功能。用PKM2抑制剂紫草素（SKN）治疗动脉粥样硬化小鼠，以评估PKM2抑制在动脉粥样硬化中的治疗潜力。氧化低密度脂蛋白（oxLDL）上调巨噬细胞中的PKM2。PKM2反过来促进巨噬细胞对oxLDL的摄取。PKM2过表达加速小鼠动脉粥样硬化。SKN阻断小鼠动脉粥样硬化的进展。PKM2加速巨噬细胞吞噬和动脉粥样硬化。靶向PKM2是动脉粥样硬化的潜在治疗方法。巨噬细胞中丙酮酸激酶肌2 （PKM2）的过度表达促进了氧化低密度脂蛋白的摄取和动脉粥样硬化，PKM2抑制剂紫草素可以减弱这一作用。
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. Global and myeloid cell‐specific PKM2 knock‐in mice with ApoE −/− background (ApoE −/− , PKM2 KI/KI and Lyz2‐cre, ApoE −/− , and PKM2 flox/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. 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. PKM2 accelerates macrophage phagocytosis and atherosclerosis. Targeting PKM2 is a potential therapy for atherosclerosis. Overexpressed pyruvate kinase muscle 2 (PKM2) in macrophage promoted oxidized low‐density lipoprotein uptake and atherosclerosis, which can be blunted by PKM2 inhibitor shikonin.