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, Dr Ryszard and Maffia, Professor Pasquale and Guzik, Professor Tomasz and Murray, Dr Eleanor and MacRitchie, Dr Neil |
| 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 > School of Cardiovascular & Metabolic Health College of Medical Veterinary and Life Sciences > School of Infection & Immunity |
| Research Centre: | College of Medical Veterinary and Life Sciences > School of Infection & Immunity > Centre for Immunobiology |
| 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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