Immunomodulation of the inflammatory response in atherosclerosis

Authors:
  • GPGijs Hm van Puijvelde
    Gijs Hm van Puijvelde
  • EWEva Ja van Wanrooij
    Eva Ja van Wanrooij
  • TEThomas van Es
    Thomas van Es
  • KHKim Habets
    Kim Habets
  • AHArnaud D Hauer
    Arnaud D Hauer
  • TBTheo Jc van Den Berkel
    Theo Jc van Den Berkel
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Abstract
Cardiovascular disease, as manifested in the formation of atherosclerotic lesions, can be described as a chronic inflammatory autoimmune-like disease that proceeds in the context of enhanced plasma lipid levels. Modulation of the immune response may therefore form a valuable therapy in addition to standardized cholesterol and blood pressure-lowering therapies. The purpose of this review is to describe a number of recent approaches to immunomodulate atherosclerosis: immunization against mediators involved in atherosclerosis, such as cytokines and modified low-density lipoprotein; intervention in cytokine pathways; intervention in co-stimulatory pathways; activation of regulatory T cells; and modulation of natural killer T cells. The most recent findings point to an important role for regulatory T cells in atherosclerotic lesion formation. The function of the regulatory T cells is modulated by chemokines and by co-stimulatory pathways, whereas the function of these cells can be strongly upregulated by anti-CD3 treatment and tolerance induction. In the near future the first exponents of this approach, such as immunization and enhancement of the function of regulatory T cells, may enter the first phase of clinical trials, and may ultimately add to the current therapies in atherosclerosis.

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