title: Epigenetic pathways in macrophages emerge as novel targets in atherosclerosis.
abstract: Atherosclerosis is a lipid-driven chronic inflammatory disorder. Monocytes and macrophages are key immune cells in the development of disease and clinical outcome. It is becoming increasingly clear that epigenetic pathways govern many aspects of monocyte and macrophage differentiation and activation. The dynamic regulation of epigenetic patterns provides opportunities to alter disease-associated epigenetic states. Therefore, pharmaceutical companies have embraced the targeting of epigenetic processes as new approaches for interventions. Particularly histone deacetylase (Hdac) inhibitors and DNA-methyltransferase inhibitors have long received attention and several of them have been approved for clinical use in relation to hematological malignancies. The key focus is still on oncology, but Alzheimer's disease, Huntington's disease and inflammatory disorders are coming in focus as well. These developments raise opportunities for the epigenetic targeting in cardiovascular disease (CVD). In this review we discuss the epigenetic regulation of the inflammatory pathways in relation to atherosclerosis with a specific attention to monocyte- and macrophage-related processes. What are the opportunities for future therapy of atherosclerosis by epigenetic interventions?
authors.affiliation: Experimental Vascular Biology, Department of Medical Biochemistry, Academic Medical Center, Meibergdreef 9, 1105 AZ Amsterdam, The Netherlands.
authors.forename: Annette E
authors.initials: AE
authors.lastname: Neele
authors.affiliation: Experimental Vascular Biology, Department of Medical Biochemistry, Academic Medical Center, Meibergdreef 9, 1105 AZ Amsterdam, The Netherlands.
authors.forename: Jan
authors.initials: J
authors.lastname: Van den Bossche
authors.affiliation: Experimental Vascular Biology, Department of Medical Biochemistry, Academic Medical Center, Meibergdreef 9, 1105 AZ Amsterdam, The Netherlands.
authors.forename: Marten A
authors.initials: MA
authors.lastname: Hoeksema
authors.affiliation: Experimental Vascular Biology, Department of Medical Biochemistry, Academic Medical Center, Meibergdreef 9, 1105 AZ Amsterdam, The Netherlands. Electronic address: m.dewinther@amc.uva.nl.
authors.forename: Menno P J
authors.initials: MP
authors.lastname: de Winther
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D050197:Atherosclerosis / Q000188:drug therapy* / Q000235:genetics* / Q000276:immunology / Q000378:metabolism; D044127:Epigenesis, Genetic / Q000187:drug effects*; D006657:Histones / Q000378:metabolism; D006801:Humans; D008264:Macrophages / Q000187:drug effects* / Q000378:metabolism*; D008969:Molecular Sequence Data; D058990:Molecular Targeted Therapy / Q000379:methods*
chemical_list: D006657:Histones
keywords: Epigenetics; Hdac inhibition; Histone methylation; Inflammation; Innate immunity; Macrophage polarization