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  • Review Article
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The immunology of atherosclerosis

Nature Reviews Nephrology volume 13, pages 368–380 (2017)Cite this article

Subjects

Key Points

  • Atherosclerotic cardiovascular disease is the leading cause of death worldwide; the disease process is accelerated in patients with chronic kidney disease

  • Hypercholesterolemia leads to accumulation of plasma LDL in the artery wall; LDL and its components elicit vascular inflammation that drives the build-up of lipid-laden atherosclerotic plaques

  • Several small populations of innate immune cells have important roles at different stages of atherosclerosis development, but macrophages are the main innate immune effector cell type in the plaque

  • T cells that respond to autoantigenic components of LDL particles orchestrate plaque development; T helper type 1 (TH1) cells promote atherosclerosis, regulatory T cells are protective and TH17 cells promote plaque stability

  • Many connections between the immune system and metabolism exist; acute inflammation induces hypertriglyceridemia, whereas chronic inflammation has more complex effects

  • Novel approaches such as anti-inflammatory therapies, T-cell-based treatments or vaccination against LDL, could potentially reduce cardiovascular inflammation and protect against the development of atherosclerosis

Abstract

Cardiovascular disease is the leading cause of death worldwide, both in the general population and among patients with chronic kidney disease (CKD). In most cases, the underlying cause of the cardiovascular event is atherosclerosis — a chronic inflammatory disease. CKD accelerates atherosclerosis via augmentation of inflammation, perturbation of lipid metabolism, and other mechanisms. In the artery wall, subendothelial retention of plasma lipoproteins triggers monocyte-derived macrophages and T helper type 1 (TH1) cells to form atherosclerotic plaques. Inflammation is initiated by innate immune reactions to modified lipoproteins and is perpetuated by TH1 cells that react to autoantigens from the apolipoprotein B100 protein of LDL. Other T cells are also active in atherosclerotic lesions; regulatory T cells inhibit pathological inflammation, whereas TH17 cells can promote plaque fibrosis. The slow build-up of atherosclerotic plaques is asymptomatic, but plaque rupture or endothelial erosion can induce thrombus formation, leading to myocardial infarction or ischaemic stroke. Targeting risk factors for atherosclerosis has reduced mortality, but a need exists for novel therapies to stabilize plaques and to treat arterial inflammation. Patients with CKD would likely benefit from such preventive measures.

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Figure 1: Innate immune responses in atherosclerosis.
Figure 2: Adaptive immunity in atherosclerosis.
Figure 3: LDL autoimmunity in atherosclerosis.

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Acknowledgements

The authors' work is supported by project grant 02738 and Linnaeus support 349-2007-8703 from the Swedish Research Council, and by grants from the Swedish Heart-Lung Foundation, the Foundation for Strategic Research (SSF), Vinnova, Stockholm County Council, King Gustav V and Queen Victoria Foundation, Prof Nanna Svartz foundation, and the European Union's Seventh Framework Programme [FP7/2007-2013] under grant agreement Athero-Flux (no 602222) and VIA (no 603131).

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  1. Department of Medicine, Center for Molecular Medicine, Karolinska University Hospital, Karolinska Institutet, Stockholm, SE-17176, Sweden

    Anton Gisterå & Göran K. Hansson

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  1. Anton Gisterå
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  2. Göran K. Hansson
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Both authors researched the data, discussed the content, wrote the manuscript and reviewed or edited the manuscript before submission.

Corresponding author

Correspondence to Göran K. Hansson.

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Competing interests

G.K.H has intellectual property rights in the area of immunotherapy for cardiovascular disease. A.G. declares no competing interests.

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Glossary

Acute phase response

The systemic inflammatory reaction to an infection or injury, including fever, tachycardia, leukocytosis and changes in circulating acute phase proteins, such as C-reactive protein.

Foam cells

Lipid-laden macrophages with a 'foamy' appearance.

Scavenger receptors

Receptors that mediate uptake of macromolecules with a negative charge, such as oxidized LDL.

Pinocytosis

A mechanism for uptake of extracellular fluids and small particles through an invagination of the cell membrane.

Germinal centres

Sites in lymphoid organs where mature B cells proliferate, differentiate, mutate their antibody genes and switch antibody classes.

Apoptotic cell immunization

A vaccination approach in which cells undergoing programmed cell death are used to evoke an immune response against oxidation-specific epitopes.

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Gisterå, A., Hansson, G. The immunology of atherosclerosis. Nat Rev Nephrol 13, 368–380 (2017). https://doi.org/10.1038/nrneph.2017.51

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