Abstract
Hypertension is a global health problem, with >1.3 billion individuals with high blood pressure worldwide. In this Review, we present an inflammatory paradigm for hypertension, emphasizing the crucial roles of immune cells, cytokines and chemokines in disease initiation and progression. T cells, monocytes, macrophages, dendritic cells, B cells and natural killer cells are all implicated in hypertension. Neoantigens, the NLRP3 inflammasome and increased sympathetic outflow, as well as cytokines (including IL-6, IL-7, IL-15, IL-18 and IL-21) and a high-salt environment, can contribute to immune activation in hypertension. The activated immune cells migrate to target organs such as arteries (especially the perivascular fat and adventitia), kidneys, the heart and the brain, where they release effector cytokines that elevate blood pressure and cause vascular remodelling, renal damage, cardiac hypertrophy, cognitive impairment and dementia. IL-17 secreted by CD4+ T helper 17 cells and γδ T cells, and interferon-γ and tumour necrosis factor secreted by immunosenescent CD8+ T cells, exert crucial effector roles in hypertension, whereas IL-10 and regulatory T cells are protective. Effector mediators impair nitric oxide bioavailability, leading to endothelial dysfunction and increased vascular contractility. Inflammatory effector mediators also alter renal sodium and water balance and promote renal fibrosis. These mechanisms link hypertension with obesity, autoimmunity, periodontitis and COVID-19. A comprehensive understanding of the immune and inflammatory mechanisms of hypertension is crucial for safely and effectively translating the findings to clinical practice.
Key points
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Hypertension is a global health challenge, affecting >1.3 billion people worldwide, and the development of this condition is closely associated with inflammatory dysregulation and immune activation.
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Immune cells such as CD8+ T cells, T helper 17 cells, regulatory T cells, monocytes, macrophages and B cells, as well as chemokines and cytokines, such as IL-17, IL-18, interferon-γ and tumour necrosis factor, have crucial roles in the immune mechanisms underlying hypertension.
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Relevant immune mechanisms can be grouped into two clusters: those involved in the regulation of the initial immune and inflammatory activation, and the immune effector mechanisms linking the immune system to end-organ mechanisms that regulate blood pressure.
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Dendritic cells presenting neoantigens, NLRP3 inflammasome activity and neuroimmune activation all contribute to the immune activation process in hypertension.
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Activated immune cells migrate to target organs, such as the arteries (especially the perivascular fat and adventitia), kidneys and brain, causing end-organ damage and elevating the blood pressure.
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A deeper understanding of the immune crosstalk between the upstream regulators and downstream effectors in hypertension will enable the application of these findings effectively in clinical settings.
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Acknowledgements
T.J.G. is funded by the European Research Council (ERC and InflammaTENSION; ERC-CoG-726318), British Heart Foundation (FS/14/49/30838 and FS/4yPhD/F/20/34127A), as part of the British Heart Foundation Centre for Research Excellence at the University of Edinburgh (RE/18/5/34216), and CVD ERA-CVD (GutBrainImmune and ImmuneHyperCog, NCBiR, Poland). T.J.G. and P.M. are supported by the British Heart Foundation (PG/19/84/34771, FS/19/56/34893A, PG/21/10541 and PG/21/10634). R.N. is funded by the Chancellor’s Fellowship at the University of Edinburgh.
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Guzik, T.J., Nosalski, R., Maffia, P. et al. Immune and inflammatory mechanisms in hypertension. Nat Rev Cardiol (2024). https://doi.org/10.1038/s41569-023-00964-1
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DOI: https://doi.org/10.1038/s41569-023-00964-1
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