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The why and how of adaptive immune responses in ischemic cardiovascular disease

Nature Cardiovascular Research volume 1, pages 431–444 (2022)Cite this article

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Abstract

Atherosclerotic cardiovascular disease is a major cause of disability and death worldwide. Most therapeutic approaches target traditional risk factors but ignore the fundamental role of the immune system. This is a huge unmet need. Recent evidence indicates that reducing inflammation may limit cardiovascular events. However, the concomitant increase in the risk of life-threatening infections is a major drawback. In this context, targeting adaptive immunity could constitute a highly effective and safer approach. In this Review, we address the why and how of the immuno-cardiovascular unit, in health and in atherosclerotic disease. We review and discuss fundamental mechanisms that ensure immune tolerance to cardiovascular tissue, and examine how their disruption promotes disease progression. We identify promising strategies to manipulate the adaptive immune system for patient benefit, including novel biologics and RNA-based vaccination strategies. Finally, we advocate for establishing a molecular classification of atherosclerosis as an important milestone in our quest to radically change the understanding and treatment of atherosclerotic disease.

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Fig. 1: The immuno-vascular unit in health and atherosclerotic disease.
Fig. 2: Adaptive immune responses in the healthy and ischemic heart.
Fig. 3: Therapeutic strategies to target adaptive immune responses.

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Acknowledgements

Z.M. is supported by the British Heart Foundation (RCAM/104, RCAM-659, RRCAM.163), the British Heart Foundation Center for Research Excellence (RE/18/1/34212), and the NIHR Cambridge Biomedical Research Centre (RG85315). C.J.B. is supported by grants from the Austrian Science Fund (FWF SFB F54) and the Vienna Science and Technology Fund (LS18-090). Z.M. and C.J.B. are supported by the Leducq Foundation (Transatlantic Network of Excellence; TNE-20CVD03).

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  1. Division of Cardiovascular Medicine, Department of Medicine, University of Cambridge, Cambridge, UK

    Ziad Mallat

  2. Unversité de Paris, and INSERM U970, Paris Cardiovascular Research Centre, Paris, France

    Ziad Mallat

  3. Department of Laboratory Medicine, Medical University of Vienna, Vienna, Austria

    Christoph J. Binder

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  2. Christoph J. Binder
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Z. M. and C. J. B. wrote the manuscript and reviewed it for important intellectual content.

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Mallat, Z., Binder, C.J. The why and how of adaptive immune responses in ischemic cardiovascular disease. Nat Cardiovasc Res 1, 431–444 (2022). https://doi.org/10.1038/s44161-022-00049-1

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