title: The epigenetic memory of monocytes and macrophages as a novel drug target in atherosclerosis.
abstract: OBJECTIVE
  Atherosclerosis is characterized by a persistent inflammation of the arterial wall. Monocyte-derived 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 histones, and of trained immunity in particular, in atherogenesis.
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  Preclinical evidence suggests that trained innate immunity may contribute to vascular wall inflammation in patients with risk factors for atherosclerosis. Epigenetic reprogramming is regulated by enzymes that are amenable to pharmacologic modulation. Therefore, this mechanism could be used to develop novel pharmacologic targets for the prevention or treatment of atherosclerotic vascular disease.
authors.affiliation: Department of Internal Medicine, Division of Experimental Medicine, Radboud University Medical Center, Nijmegen, the Netherlands.
authors.forename: Siroon
authors.initials: S
authors.lastname: Bekkering
authors.affiliation: Department of Internal Medicine, Division of Experimental Medicine, Radboud University Medical Center, Nijmegen, the Netherlands.
authors.forename: Leo A B
authors.initials: LA
authors.lastname: Joosten
authors.affiliation: Department of Internal Medicine, Division of Experimental Medicine, Radboud University Medical Center, Nijmegen, the Netherlands.
authors.forename: Jos W M
authors.initials: JW
authors.lastname: van der Meer
authors.affiliation: Department of Internal Medicine, Division of Experimental Medicine, Radboud University Medical Center, Nijmegen, the Netherlands.
authors.forename: Mihai G
authors.initials: MG
authors.lastname: Netea
authors.affiliation: Department of Internal Medicine, Division of Vascular Medicine, Radboud University Medical Center, Nijmegen, the Netherlands; Department of Pharmacology-Toxicology, Radboud University Medical Center, Nijmegen, the Netherlands. Electronic address: niels.riksen@radboudumc.nl.
authors.forename: Niels P
authors.initials: NP
authors.lastname: Riksen
mesh_terms: D050197:Atherosclerosis / Q000188:drug therapy* / Q000276:immunology; D016207:Cytokines / Q000276:immunology; D006801:Humans; D007113:Immunity, Innate; D007249:Inflammation / Q000276:immunology; D008264:Macrophages / Q000378:metabolism*; D009000:Monocytes / Q000378:metabolism*; D058226:Plaque, Atherosclerotic / Q000188:drug therapy / Q000276:immunology
chemical_list: D016207:Cytokines
keywords: atherosclerosis; epigenetic modifications; inflammation; monocytes