Siroon Bekkering1, Leo A B Joosten1, Jos W M van der Meer1, Mihai G Netea1, Niels P Riksen2. 1. Department of Internal Medicine, Division of Experimental Medicine, Radboud University Medical Center, Nijmegen, the Netherlands. 2. 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.
Abstract
PURPOSE: 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. 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. IMPLICATIONS: 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.
PURPOSE: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. 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. IMPLICATIONS: 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: Willem J M Mulder; Jordi Ochando; Leo A B Joosten; Zahi A Fayad; Mihai G Netea Journal: Nat Rev Drug Discov Date: 2019-07 Impact factor: 84.694
Authors: Kathryn A Arnold; John E Blair; Jonathan D Paul; Atman P Shah; Sandeep Nathan; Francis J Alenghat Journal: Exp Physiol Date: 2019-07-25 Impact factor: 2.969
Authors: Mihai G Netea; Leo A B Joosten; Eicke Latz; Kingston H G Mills; Gioacchino Natoli; Hendrik G Stunnenberg; Luke A J O'Neill; Ramnik J Xavier Journal: Science Date: 2016-04-21 Impact factor: 47.728
Authors: Renate M Hoogeveen; Matthias Nahrendorf; Niels P Riksen; Mihai G Netea; Menno P J de Winther; Esther Lutgens; Børge G Nordestgaard; Michel Neidhart; Erik S G Stroes; Alberico L Catapano; Siroon Bekkering Journal: Eur Heart J Date: 2018-10-07 Impact factor: 29.983
Authors: Niels A J Cremers; Martijn H J van den Bosch; Stephanie van Dalen; Irene Di Ceglie; Giuliana Ascone; Fons van de Loo; Marije Koenders; Peter van der Kraan; Annet Sloetjes; Thomas Vogl; Johannes Roth; Edwin J W Geven; Arjen B Blom; Peter L E M van Lent Journal: Arthritis Res Ther Date: 2017-09-29 Impact factor: 5.156