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

Michael Lacy, Dorothee Atzler, Rongqi Liu, Menno de Winther, Christian Weber, Esther Lutgens

Research output: Contribution to journalReview articlepeer-review

Abstract

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.

Original languageEnglish (US)
Pages (from-to)50-62
Number of pages13
JournalPharmacology and Therapeutics
Volume193
DOIs
StatePublished - Jan 2019

Keywords

  • Atherosclerosis
  • CANTOS
  • CVD
  • Epigenetics
  • Lipids
  • oxLDL
  • Trained immunity

ASJC Scopus subject areas

  • Pharmacology
  • Pharmacology (medical)

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