Pdcd4 deficiency enhances macrophage lipoautophagy and attenuates foam cell formation and atherosclerosis in mice

Cell Death & Disease
L WangL Zhang

Abstract

Macrophage foam cells, a major component of the atherosclerotic lesion, have vital roles in the development of atherosclerosis. Lipoautophagy, a type of autophagy characterized by selective delivery of lipid droplet for lysosomal degradation, may impact atherosclerosis by regulating macrophage foam cell formation. Previously, we reported that programmed cell death 4 (PDCD4), a tumor suppressor, negatively regulated autophagy in tumor cells. However, its roles in macrophage lipoautophagy, foam cell formation and atherosclerosis remain to be established. Here we found that Pdcd4 deficiency clearly improved oxidized low-density lipoproteins-impaired autophagy efflux, promoted autophagy-mediated lipid breakdown in murine macrophages and thus prevented macrophage conversion into foam cells. Importantly, Pdcd4 deficiency in mice significantly upregulated macrophage autophagy in local plaques along with attenuated lipid accumulation and atherosclerotic lesions in high-fat-fed Apolipoprotein E knockout mice. Bone marrow transplantation experiment demonstrated that PDCD4-mediated autophagy in hematopoietic cells contributed to the development of atherosclerosis. These results indicate that endogenous PDCD4 promotes for macrophage foam c...Continue Reading

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Jan 20, 2017·Cell Death & Disease·Jiayuan Y KouLiming M Yang
Apr 3, 2019·Experimental and Therapeutic Medicine·Yuhong GaoYanping Chen
Nov 16, 2016·Mediators of Inflammation·Jinshan YeLixia Yang
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Oct 27, 2020·Cell Death and Differentiation·Xiaotong ChenLining Zhang
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Apr 17, 2021·The Biochemical Journal·Md Khurshidul ZahidShaikh Mizanoor Rahman
Jul 5, 2021·Toxicology·Ida FloranceNatarajan Chandrasekaran
Apr 9, 2021·Biochemistry and Cell Biology = Biochimie Et Biologie Cellulaire·Ezra Kombo OsoroShemin Lu

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Methods Mentioned

BETA
PCR
electrophoresis

Software Mentioned

Image Proplus
GraphPad Prism
GraphPad

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