title: Atherosclerosis and interferon-γ: new insights and therapeutic targets.
abstract: Atherosclerosis is considered to be a chronic inflammatory disease of the arterial wall. Atherogenesis is accompanied by local production and release of inflammatory mediators, for which the macrophage is a major source. The proinflammatory cytokine, interferon (IFN)-γ derived from T cells, is expressed at high levels in atherosclerotic lesions. IFN-γ is the classic macrophage-activating factor, vital for both innate and adaptive immunity. It primes macrophages to produce chemokines and cytotoxic molecules and induces expression of genes that regulate lipid uptake. IFN-γ is a key trigger for the formation and release of reactive oxygen species. IFN-γ has important effects on endothelial cells, promoting expression of adhesion molecules. Atherogenic effects of IFN-γ have been shown in murine models where exogenous administration enhances atherosclerotic lesion formation while knockout of IFN-γ or its receptor reduces lesion size. IFN-γ signaling is largely mediated by a Janus kinase (JAK) to signal transduction and activator of transcription (STAT)1 cytosolic factor pathway. A clear understanding of IFN-γ effects on atherogenesis should enable development of novel targeted interventions for clinical use in the prevention and treatment of atherosclerosis. This review will discuss the actions of the cytokine IFN-γ and its complex effects on cells involved in atherosclerosis.
authors.affiliation: Department of Medicine, Winthrop Research Institute, Winthrop-University Hospital, 222 Station Plaza North, Mineola, NY 11501.
authors.forename: Iryna
authors.initials: I
authors.lastname: Voloshyna
authors.affiliation: Department of Medicine, Winthrop Research Institute, Winthrop-University Hospital, 222 Station Plaza North, Mineola, NY 11501.
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Littlefield
authors.affiliation: Department of Medicine, Winthrop Research Institute, Winthrop-University Hospital, 222 Station Plaza North, Mineola, NY 11501. Electronic address: areiss@winthrop.org.
authors.forename: Allison B
authors.initials: AB
authors.lastname: Reiss
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents / Q000627:therapeutic use*; D050197:Atherosclerosis / Q000188:drug therapy* / Q000276:immunology / Q000378:metabolism; D002317:Cardiovascular Agents / Q000627:therapeutic use*; D015195:Drug Design; D006801:Humans; D018836:Inflammation Mediators / Q000037:antagonists & inhibitors* / Q000378:metabolism; D007371:Interferon-gamma / Q000037:antagonists & inhibitors* / Q000378:metabolism; D058990:Molecular Targeted Therapy; D015398:Signal Transduction / Q000187:drug effects
chemical_list: D000893:Anti-Inflammatory Agents; D002317:Cardiovascular Agents; D018836:Inflammation Mediators; D007371:Interferon-gamma
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