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

Abstract 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...

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Bibliographic Details
Published in:Cardiovascular research 2021-11, Vol.117 (13), p.2589-2609
Main Authors: Murray, Eleanor C, Nosalski, Ryszard, MacRitchie, Neil, Tomaszewski, Maciej, Maffia, Pasquale, Harrison, David G, Guzik, Tomasz J
Format: Article
Language:English
Subjects:
Animals
Anti-Inflammatory Agents - therapeutic use
Antihypertensive Agents - therapeutic use
Blood Pressure - drug effects
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Humans
Hypertension - drug therapy
Hypertension - genetics
Hypertension - immunology
Hypertension - physiopathology
Immunomodulating Agents - therapeutic use
Immunosuppressive Agents - therapeutic use
Inflammation - drug therapy
Inflammation - genetics
Inflammation - immunology
Inflammation - physiopathology
Inflammation Mediators - antagonists & inhibitors
Inflammation Mediators - immunology
Invited Spotlight Reviews
Molecular Targeted Therapy
Signal Transduction
Translational Research, Biomedical
Tumor Necrosis Factor Inhibitors - therapeutic use
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Summary:Abstract 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. Graphical Abstract
ISSN:0008-6363
1755-3245
DOI:10.1093/cvr/cvab330