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Anti-inflammatory therapies for atherosclerosis

Nature Reviews Cardiology volume 12, pages 199–211 (2015)Cite this article

Subjects

Key Points

  • Atherosclerosis is characterized by lipid deposition and chronic inflammation, associated with immune activation and the induction of inflammatory mediators and signalling pathways

  • Putative therapeutic strategies specifically targeting chronic inflammation in atherosclerosis include classic anti-inflammatory drugs, biologic therapies targeting cytokines and chemokines, and small molecule enzyme inhibitors and receptor antagonists

  • Inducing immune tolerance through vaccination against atherosclerosis-associated immunogens can potentially offer an additional strategy for protection against atherosclerosis

  • Evidence in support of the use of anti-inflammatory therapies for atherosclerosis is mainly based on either observational or small interventional studies to evaluate surrogate markers of disease activity

  • Randomized controlled studies to evaluate the effect of specific anti-inflammatory strategies on cardiovascular outcomes are ongoing and might lead the way for additional therapeutic strategies

Abstract

The view of atherosclerosis as an inflammatory disease has emerged from observations of immune activation and inflammatory signalling in human atherosclerotic lesions, from the definition of inflammatory biomarkers as independent risk factors for cardiovascular events, and from evidence of low-density lipoprotein-induced immune activation. Studies in animal models of hyperlipidaemia have also supported the beneficial effects of countering inflammation to delay atherosclerosis progression. Specific inflammatory pathways with relevance to human diseases have been identified, and inhibitors of these pathways are either already in use for the treatment of other diseases, or are under development and evaluation. These include 'classic' drugs (such as allopurinol, colchicine, and methotrexate), biologic therapies (for example tumour necrosis factor inhibitors and IL-1 neutralization), as well as targeting of lipid mediators (such as phospholipase inhibitors and antileukotrienes) or intracellular pathways (inhibition of NADPH oxidase, p38 mitogen-activated protein kinase, or phosphodiesterase). The evidence supporting the use of anti-inflammatory therapies for atherosclerosis is mainly based on either observational or small interventional studies evaluating surrogate markers of disease activity. Nevertheless, these data are crucial to understand the role of inflammation in atherosclerosis, and to design randomized controlled studies to evaluate the effect of specific anti-inflammatory strategies on cardiovascular outcomes.

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Figure 1: Inflammation pathways with potential roles in atherosclerosis.
Figure 2: Phospholipases and lipid mediators of inflammation in atherosclerosis.

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Acknowledgements

The authors are supported by the Swedish Research Council, the Swedish Heart and Lung Foundation, the Stockholm County Council, the European Commission, and the Linnaeus Center of Excellence for Research on Inflammation and Cardiovascular disease (CERIC).

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  1. Department of Medicine, Experimental Cardiovascular Research Unit, Center for Molecular Medicine, Karolinska Institutet, L8:03, Karolinska University Hospital, Stockholm, SE-171 76, Sweden

    Magnus Bäck & Göran K. Hansson

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Both authors researched the data for the article, provided substantial contributions to discussions of its content, wrote the article, and reviewed and/or edited the manuscript before submission.

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Bäck, M., Hansson, G. Anti-inflammatory therapies for atherosclerosis. Nat Rev Cardiol 12, 199–211 (2015). https://doi.org/10.1038/nrcardio.2015.5

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