Interactions between dyslipidemia and the immune system and their relevance as putative therapeutic targets in atherosclerosis

Cardiovascular disease (CVD) continues to be a leading cause of death worldwide with atherosclerosis being the major underlying pathology. The interplay between lipids and immune cells is believed to be a driving force in the chronic inflammation of the arterial wall during atherogenesis. Atheroscle...

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Bibliographic Details
Published in:Pharmacology & therapeutics (Oxford) 2019-01, Vol.193, p.50-62
Main Authors: Lacy, Michael, Atzler, Dorothee, Liu, Rongqi, de Winther, Menno, Weber, Christian, Lutgens, Esther
Format: Article
Language:English
Subjects:
Animals
Atherosclerosis
Atherosclerosis - drug therapy
Atherosclerosis - immunology
CANTOS
CVD
Dyslipidemias - immunology
Epigenetics
Humans
Lipids
oxLDL
Trained immunity
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Summary:Cardiovascular disease (CVD) continues to be a leading cause of death worldwide with atherosclerosis being the major underlying pathology. The interplay between lipids and immune cells is believed to be a driving force in the chronic inflammation of the arterial wall during atherogenesis. Atherosclerosis is initiated as lipid particles accumulate and become trapped in vessel walls. The subsequent immune response, involving both adaptive and immune cells, progresses plaque development, which may be exacerbated under dyslipidemic conditions. Broad evidence, especially from animal models, clearly demonstrates the effect of lipids on immune cells from their development in the bone marrow to their phenotypic switching in circulation. Interestingly, recent research has also shown a long-lasting epigenetic signature from lipids on immune cells. Traditionally, cardiovascular therapies have approached atherosclerosis through lipid-lowering medications because, until recently, anti-inflammatory therapies have been largely unsuccessful in clinical trials. However, the recent Canakinumab Antiinflammatory Thrombosis Outcomes Study (CANTOS) provided pivotal support of the inflammatory hypothesis of atherosclerosis in man spurring on anti-inflammatory strategies to treat atherosclerosis. In this review, we describe the interactions between lipids and immune cells along with their specific outcomes as well as discuss their future perspective as potential cardiovascular targets.
ISSN:0163-7258
1879-016X
DOI:10.1016/j.pharmthera.2018.08.012