The Epigenetic Memory of Monocytes and Macrophages as a Novel Drug Target in Atherosclerosis

被引:59
作者
Bekkering, Siroon [1 ]
Joosten, Leo A. B. [1 ]
van der Meer, Jos W. M. [1 ]
Netea, Mihai G.
Riksen, Niels P. [2 ,3 ]
机构
[1] Radboud Univ Nijmegen, Med Ctr, Dept Internal Med, Div Expt Med, NL-6500 HB Nijmegen, Netherlands
[2] Radboud Univ Nijmegen, Med Ctr, Dept Internal Med, Div Vasc Med, NL-6500 HB Nijmegen, Netherlands
[3] Radboud Univ Nijmegen, Med Ctr, Dept Pharmacol Toxicol, NL-6500 HB Nijmegen, Netherlands
基金
欧洲研究理事会;
关键词
atherosclerosis; epigenetic modifications; inflammation; monocytes; LOW-DENSITY-LIPOPROTEIN; MEDIATED HISTONE MODIFICATIONS; CARDIOVASCULAR RISK; GENE-EXPRESSION; INNATE IMMUNITY; INFLAMMATION; DISEASE; HYPERCHOLESTEROLEMIA; DEACETYLASES; METHYLATION;
D O I
10.1016/j.clinthera.2015.01.008
中图分类号
R9 [药学];
学科分类号
1007 ;
摘要
Purpose: Atherosclerosis is characterized by a persistent inflammation of the arterial wall. Monocytederived macrophages are the most abundant immune cells in atherosclerotic plaques. After, stimulation, monocytes can adopt a long-term proinflammatory phenotype. This nonspecific memory of innate immune cells is mediated by epigenetic reprogramming and has recently been termed "trained innate immunity." The goal of this study was to describe the potential role of trained immunity in the development of atherosclerosis and to discuss the potential clinical implications of this concept. Methods: We performed a comprehensive. literature search (PubMed) on the :role of epigenetic programming of hisiones, and of trained immunity in particular, in atherogenesis. Findings: In vitro studies demonstrate that:modified LDL particles can induce a long-term proinflammatory phenotype in monocytes/macrophages by epigenetic reprogramming at the level of histone methylation. This scenario is associated with increased production of proatherogenic cytokines and chemokines and increased formation of foam cells. (C) 2015 Elsevier HS journals, Inc. All rights reserved.
引用
收藏
页码:914 / 923
页数:10
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