Overexpressed PKM2 promotes macrophage phagocytosis and atherosclerosis
Xiaochen Gai, Fangming Liu, Yuting Wu, Baohui Zhang, Bufu Tang, Kezhuo Shang, Lianmei Wang, Haihong Zhang, Haihong Zhang, Yixin Chen, Shuhui Yang, Weiwei Deng, Peng Li, Jing Wang, Hongbing Zhang, Hongbing Zhang
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: ) 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.