Immune and inflammatory mechanisms in hypertension

Guzik, T. J., Nosalski, R., Maffia, P. and Drummond, G. R. (2024) Immune and inflammatory mechanisms in hypertension. Nature Reviews Cardiology, (doi: 10.1038/s41569-023-00964-1) (PMID:38172242) (Early Online Publication)

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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.

Item Type:Articles
Additional Information: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.
Status:Early Online Publication
Glasgow Author(s) Enlighten ID:Guzik, Professor Tomasz and Nosalski, Dr Ryszard and Maffia, Professor Pasquale
Authors: Guzik, T. J., Nosalski, R., Maffia, P., and Drummond, G. R.
College/School:College of Medical Veterinary and Life Sciences > School of Cardiovascular & Metabolic Health
College of Medical Veterinary and Life Sciences > School of Infection & Immunity
Journal Name:Nature Reviews Cardiology
Publisher:Nature Research
ISSN (Online):1759-5010
Published Online:03 January 2024
Copyright Holders:Copyright © 2024 Springer Nature Limited
First Published:First published in Nature Reviews Cardiology 2024
Publisher Policy:Reproduced in accordance with the copyright policy of the publisher

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Project CodeAward NoProject NamePrincipal InvestigatorFunder's NameFunder RefLead Dept
170444Assessing the contribution of microRNA to in-stent restenosisTomasz GuzikBritish Heart Foundation (BHF)FS/14/49/30838School of Cardiovascular & Metabolic Health
309321BHF 4Yr PhD Studentship Award 2109Rhian TouyzBritish Heart Foundation (BHF)FS/19/56/34893SCMH - Cardiovascular & Metabolic Health
313479Defining AXL Role in AtherosclerosisPasquale MaffiaBritish Heart Foundation (BHF)PG/21/10541SCMH - Cardiovascular & Metabolic Health
314413Defining the IL-21/IL-21 receptor axis role(s) in atherosclerosisPasquale MaffiaBritish Heart Foundation (BHF)PG/21/10634SCMH - Cardiovascular & Metabolic Health