The anti-atherosclerosis effect and molecular mechanism of AMPKα1 by polarizing monocytes to an M2 phenotype via cell-intrinsic lysosomal lipolysis

IF 2.3 4区医学 Q2 CARDIAC & CARDIOVASCULAR SYSTEMS

Cardiovascular Pathology Pub Date : 2025-05-10 DOI:10.1016/j.carpath.2025.107742

Jing Wang , Yahui Zhang , Caixing Cao , Jiale Hua , Li Xing , Changxin Wu

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引用次数: 0

Abstract

Regulating the differentiation of monocytes into M2 macrophages can promote the regression of Atherosclerosis (AS) plaque. However, the key molecules regulating the differentiation of monocytes to M2 are unknown. In this study, we reported that adenosine-activated protein kinase α1 (AMPKα1) plays an anti-AS role by polarizing monocytes to an M2 phenotype via promoting fatty acid oxidation (FAO). AMPKα1 enhances the decomposition of cholesterol esters by increasing lysosomal acid lipase expression to provide fatty acids for FAO. Furthermore, AMPKα1 can induce lysosomal biogenesis and enhance lipolysis by promoting the transcription factor EB (TFEB) expression and facilitating TFEB nuclear translocation. In conclusion, AMPKα1 enhances the decomposition of cholesterol esters by increasing lysosomal acid lipase expression to produce fatty acids, which may represent a mechanism to promote FAO and inflammatory monocytes differentiation towards M2 phenotype.

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AMPKα1通过细胞内溶酶体脂解将单核细胞极化为M2型的抗动脉粥样硬化作用及其分子机制。

调节单核细胞向M2巨噬细胞的分化可促进动脉粥样硬化斑块的消退。然而，调控单核细胞向M2分化的关键分子尚不清楚。在这项研究中，我们报道了腺苷活化蛋白激酶α1 （AMPKα1）通过促进脂肪酸氧化（FAO）将单核细胞极化为M2表型，从而发挥抗as作用。AMPKα1通过增加溶酶体酸性脂肪酶的表达来促进胆固醇酯的分解，为FAO提供脂肪酸。AMPKα1通过促进转录因子EB （TFEB）的表达和促进TFEB核易位，诱导溶酶体生物发生，促进脂肪分解。综上所述，AMPKα1通过增加溶酶体酸性脂肪酶的表达来促进胆固醇酯的分解产生脂肪酸，这可能是促进FAO和炎性单核细胞向M2表型分化的机制之一。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Cardiovascular Pathology 医学-病理学

CiteScore

7.50

自引率

2.70%

发文量

审稿时长

18 days

期刊介绍： Cardiovascular Pathology is a bimonthly journal that presents articles on topics covering the entire spectrum of cardiovascular disease. The Journal''s primary objective is to publish papers on disease-oriented morphology and pathogenesis from clinicians and scientists in the cardiovascular field. Subjects covered include cardiovascular biology, prosthetic devices, molecular biology and experimental models of cardiovascular disease.