Therapeutic targeting of inflammation in hypertension: from novel mechanisms to translational perspective

Murray, E. C. , Nosalski, R., MacRitchie, N., Tomaszewski, M., Maffia, P. , Harrison, D. G. and Guzik, T. J. (2021) Therapeutic targeting of inflammation in hypertension: from novel mechanisms to translational perspective. Cardiovascular Research, 117(13), pp. 2589-2609. (doi: 10.1093/cvr/cvab330) (PMID:34698811)

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Abstract

Animal models, human observational and genetic studies have shown that immune and inflammatory mechanisms play a key role in hypertension and its complications. We review the effects of immunomodulatory interventions on blood pressure, target organ damage and cardiovascular risk in humans. In experimental and small clinical studies both non-specific immunomodulatory approaches, such as mycophenolate mofetil and methotrexate, and medications targeting T and B lymphocytes, such as tacrolimus, cyclosporine, everolimus, rituximab, lower blood pressure and reduce organ damage. Mechanistically targeted immune interventions include isolevuglandin (isoLG) scavengers to prevent neo-antigen formation, co-stimulation blockade (abatacept, belatacept), and anti-cytokine therapies (secukinumab, tocilizumab, canakinumab, TNF-α inhibitors). In many studies, trial designs have been complicated by a lack of blood pressure related endpoints, inclusion of largely normotensive study populations, polypharmacy, and established comorbidities. Among a wide range of interventions reviewed, TNF-α inhibitors have provided the most robust evidence of blood pressure lowering. Treatment of periodontitis also appears to deliver non-pharmacological antihypertensive effects. Evidence of immunomodulatory drugs influencing hypertension-mediated organ damage are discussed. Animal model, observational studies, and trial data in humans support the therapeutic potential of immune targeted therapies in blood pressure lowering and in hypertension-mediated organ damage. Targeted studies are now needed to address their effects on blood pressure in hypertensive individuals.

Item Type:Articles
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:Nosalski, Mr Ryszard and Maffia, Professor Pasquale and Guzik, Professor Tomasz and MacRitchie, Dr Neil and Murray, Dr Eleanor
Authors: Murray, E. C., Nosalski, R., MacRitchie, N., Tomaszewski, M., Maffia, P., Harrison, D. G., and Guzik, T. J.
College/School:College of Medical Veterinary and Life Sciences > Institute of Cardiovascular and Medical Sciences
College of Medical Veterinary and Life Sciences > Institute of Infection Immunity and Inflammation
Journal Name:Cardiovascular Research
Publisher:Oxford University Press
ISSN:0008-6363
ISSN (Online):1755-3245
Published Online:26 October 2021
Copyright Holders:Copyright © 2021 The Authors
First Published:First published in Cardiovascular Research 117(13): 2589-2609
Publisher Policy:Reproduced under a Creative Commons licence

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Project CodeAward NoProject NamePrincipal InvestigatorFunder's NameFunder RefLead Dept
190580Defining innate and adaptive immune functions of plasmacytoid dendritic cells in atherosclerosis.Pasquale MaffiaBritish Heart Foundation (BHF)PG/12/81/29897III - Immunology
308639Defining the individual and integrated roles of inflammatory chemokine receptors (iCCRs) in atherosclerosisPasquale MaffiaBritish Heart Foundation (BHF)PG/19/84/34771CAMS - Cardiovascular Science
190814BHF centre of excellenceRhian TouyzBritish Heart Foundation (BHF)RE/13/5/30177Institute of Cardiovascular & Medical Sciences
173707Institutional Strategic Support Fund (2016)Anna DominiczakWellcome Trust (WELLCOTR)204820/Z/16/ZInstitute of Cardiovascular & Medical Sciences