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

Both animal models and 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....

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Autores principales: Murray, Eleanor C, Nosalski, Ryszard, MacRitchie, Neil, Tomaszewski, Maciej, Maffia, Pasquale, Harrison, David G, Guzik, Tomasz J
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Oxford University Press 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9825256/
https://www.ncbi.nlm.nih.gov/pubmed/34698811
http://dx.doi.org/10.1093/cvr/cvab330
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author Murray, Eleanor C
Nosalski, Ryszard
MacRitchie, Neil
Tomaszewski, Maciej
Maffia, Pasquale
Harrison, David G
Guzik, Tomasz J
author_facet Murray, Eleanor C
Nosalski, Ryszard
MacRitchie, Neil
Tomaszewski, Maciej
Maffia, Pasquale
Harrison, David G
Guzik, Tomasz J
author_sort Murray, Eleanor C
collection PubMed
description Both animal models and 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, and rituximab, lower blood pressure and reduce organ damage. Mechanistically targeted immune interventions include isolevuglandin scavengers to prevent neo-antigen formation, co-stimulation blockade (abatacept, belatacept), and anti-cytokine therapies (e.g. 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 anti-hypertensive effects. Evidence of immunomodulatory drugs influencing hypertension-mediated organ damage are also discussed. The reviewed animal models, 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.
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spelling pubmed-98252562023-01-09 Therapeutic targeting of inflammation in hypertension: from novel mechanisms to translational perspective Murray, Eleanor C Nosalski, Ryszard MacRitchie, Neil Tomaszewski, Maciej Maffia, Pasquale Harrison, David G Guzik, Tomasz J Cardiovasc Res Invited Spotlight Reviews Both animal models and 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, and rituximab, lower blood pressure and reduce organ damage. Mechanistically targeted immune interventions include isolevuglandin scavengers to prevent neo-antigen formation, co-stimulation blockade (abatacept, belatacept), and anti-cytokine therapies (e.g. 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 anti-hypertensive effects. Evidence of immunomodulatory drugs influencing hypertension-mediated organ damage are also discussed. The reviewed animal models, 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. Oxford University Press 2021-10-26 /pmc/articles/PMC9825256/ /pubmed/34698811 http://dx.doi.org/10.1093/cvr/cvab330 Text en © The Author(s) 2021. Published by Oxford University Press on behalf of the European Society of Cardiology. https://creativecommons.org/licenses/by/4.0/This is an Open Access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/), which permits unrestricted reuse, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Invited Spotlight Reviews
Murray, Eleanor C
Nosalski, Ryszard
MacRitchie, Neil
Tomaszewski, Maciej
Maffia, Pasquale
Harrison, David G
Guzik, Tomasz J
Therapeutic targeting of inflammation in hypertension: from novel mechanisms to translational perspective
title Therapeutic targeting of inflammation in hypertension: from novel mechanisms to translational perspective
title_full Therapeutic targeting of inflammation in hypertension: from novel mechanisms to translational perspective
title_fullStr Therapeutic targeting of inflammation in hypertension: from novel mechanisms to translational perspective
title_full_unstemmed Therapeutic targeting of inflammation in hypertension: from novel mechanisms to translational perspective
title_short Therapeutic targeting of inflammation in hypertension: from novel mechanisms to translational perspective
title_sort therapeutic targeting of inflammation in hypertension: from novel mechanisms to translational perspective
topic Invited Spotlight Reviews
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9825256/
https://www.ncbi.nlm.nih.gov/pubmed/34698811
http://dx.doi.org/10.1093/cvr/cvab330
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