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Myocardial infarction drives trained immunity of monocytes, accelerating atherosclerosis

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机构： [1]Department of Cardiology, Zhongshan Hospital, Fudan University, Shanghai Institute of Cardiovascular Diseases, 180 Fenglin Road, Shanghai 200032, China. [2]Key Laboratory of Viral Heart Diseases, National Health Commission, Shanghai, China. [3]Key Laboratory of Viral Heart Diseases, Chinese Academy of Medical Sciences, Shanghai, China. [4]National Clinical Research Center for Interventional Medicine, Shanghai, China. [5]Institute of Cardiovascular Diseases, Tongren Hospital, Shanghai Jiao Tong University School of Medicine, 1111 XianXia Road, Shanghai, China. [6]Department of Cardiology, Songjiang Hospital Affiliated to Shanghai Jiao Tong University School of Medicine (Preparatory Stage), Shanghai 201600, China. [7]Department of Physiology and Biophysics, University of Mississippi Medical Center, Jackson, MS, USA. [8]Institutes of Biomedical Sciences, Fudan University, Shanghai, China. [9]Collaborative Innovation Centre of Regenerative Medicine and Medical Bioresource Development and Application Co-constructed by the Province and Ministry, Guangxi Medical University, Nanning, Guangxi, China.

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关键词： Myocardial infarction Atherosclerosis Trained immunity Macrophages Monocytes Epigenetics

摘要：

Survivors of acute coronary syndromes face an elevated risk of recurrent atherosclerosis-related vascular events despite advanced medical treatments. The underlying causes remain unclear. This study aims to investigate whether myocardial infarction (MI)-induced trained immunity in monocytes could sustain proatherogenic traits and expedite atherosclerosis.Apolipoprotein-E deficient (ApoE-/-) mice and adoptive bone marrow transfer chimeric mice underwent MI or myocardial ischaemia-reperfusion (IR). A subsequent 12-week high-fat diet (HFD) regimen was implemented to elucidate the mechanism behind monocyte trained immunity. In addition, classical monocytes were analysed by flow cytometry in the blood of enrolled patients.In MI and IR mice, blood monocytes and bone marrow-derived macrophages exhibited elevated spleen tyrosine kinase (SYK), lysine methyltransferase 5A (KMT5A), and CCHC-type zinc finger nucleic acid-binding protein (CNBP) expression upon exposure to a HFD or oxidized LDL (oxLDL) stimulation. MI-induced trained immunity was transmissible by transplantation of bone marrow to accelerate atherosclerosis in naive recipients. KMT5A specifically recruited monomethylation of Lys20 of histone H4 (H4K20me) to the gene body of SYK and synergistically transactivated SYK with CNBP. In vivo small interfering RNA (siRNA) inhibition of KMT5A or CNBP potentially slowed post-MI atherosclerosis. Sympathetic denervation with 6-hydroxydopamine reduced atherosclerosis and inflammation after MI. Classical monocytes from ST-elevation MI (STEMI) patients with advanced coronary lesions expressed higher SYK and KMT5A gene levels.The findings underscore the crucial role of monocyte trained immunity in accelerated atherosclerosis after MI, implying that SYK in blood classical monocytes may serve as a predictive factor for the progression of atherosclerosis in STEMI patients.© The Author(s) 2023. Published by Oxford University Press on behalf of the European Society of Cardiology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

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出版当年[2023]版：

大类 | 1 区

医学

小类 | 1 区心脏和心血管系统

最新[2023]版：

大类 | 1 区

医学

小类 | 1 区心脏和心血管系统

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出版当年[2022]版：

Q1 CARDIAC & CARDIOVASCULAR SYSTEMS

最新[2023]版：

Q1 CARDIAC & CARDIOVASCULAR SYSTEMS

影响因子： 38.1 最新[2023版] 32.8 最新五年平均 39.3 出版当年[2022版] 31.4 出版当年五年平均 35.855 出版前一年[2021版] 38.1 出版后一年[2023版]

第一作者：

第一作者机构： [1]Department of Cardiology, Zhongshan Hospital, Fudan University, Shanghai Institute of Cardiovascular Diseases, 180 Fenglin Road, Shanghai 200032, China. [2]Key Laboratory of Viral Heart Diseases, National Health Commission, Shanghai, China. [3]Key Laboratory of Viral Heart Diseases, Chinese Academy of Medical Sciences, Shanghai, China. [4]National Clinical Research Center for Interventional Medicine, Shanghai, China.

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通讯作者：

通讯机构： [1]Department of Cardiology, Zhongshan Hospital, Fudan University, Shanghai Institute of Cardiovascular Diseases, 180 Fenglin Road, Shanghai 200032, China. [2]Key Laboratory of Viral Heart Diseases, National Health Commission, Shanghai, China. [3]Key Laboratory of Viral Heart Diseases, Chinese Academy of Medical Sciences, Shanghai, China. [4]National Clinical Research Center for Interventional Medicine, Shanghai, China. [8]Institutes of Biomedical Sciences, Fudan University, Shanghai, China.

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Myocardial infarction drives trained immunity of monocytes, accelerating atherosclerosis

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