The Immunomodulatory Effects of Statins on Macrophages

Statins are 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors used worldwide to manage dyslipidaemia and thus limit the development of atherosclerotic disease and its complications. These atheroprotective drugs are now known to exert pleiotropic actions outside of their cholestero...

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Main Authors: Alanah Sheridan, Caroline P. D. Wheeler-Jones, Matthew C. Gage
Format: Article
Language:English
Published: MDPI AG 2022-04-01
Series:Immuno
Subjects:
Online Access:https://www.mdpi.com/2673-5601/2/2/21
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author Alanah Sheridan
Caroline P. D. Wheeler-Jones
Matthew C. Gage
author_facet Alanah Sheridan
Caroline P. D. Wheeler-Jones
Matthew C. Gage
author_sort Alanah Sheridan
collection DOAJ
description Statins are 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors used worldwide to manage dyslipidaemia and thus limit the development of atherosclerotic disease and its complications. These atheroprotective drugs are now known to exert pleiotropic actions outside of their cholesterol-lowering activity, including altering immune cell function. Macrophages are phagocytic leukocytes that play critical functional roles in the pathogenesis of atherosclerosis and are directly targeted by statins. Early studies documented the anti-inflammatory effects of statins on macrophages, but emerging evidence suggests that these drugs can also enhance pro-inflammatory macrophage responses, creating an unresolved paradox. This review comprehensively examines the in vitro, in vivo, and clinical literature to document the statin-induced changes in macrophage polarization and immunomodulatory functions, explore the underlying mechanisms involved, and offer potential explanations for this paradox. A better understanding of the immunomodulatory actions of statins on macrophages should pave the way for the development of novel therapeutic approaches to manage atherosclerosis and other chronic diseases and conditions characterised by unresolved inflammation.
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spelling doaj.art-7c773aa131734e8cb4893f10390a33512023-11-23T17:09:04ZengMDPI AGImmuno2673-56012022-04-012231734310.3390/immuno2020021The Immunomodulatory Effects of Statins on MacrophagesAlanah Sheridan0Caroline P. D. Wheeler-Jones1Matthew C. Gage2Department of Comparative Biomedical Sciences, Royal Veterinary College, 4 Royal College Street, London NW1 0TU, UKDepartment of Comparative Biomedical Sciences, Royal Veterinary College, 4 Royal College Street, London NW1 0TU, UKDepartment of Comparative Biomedical Sciences, Royal Veterinary College, 4 Royal College Street, London NW1 0TU, UKStatins are 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors used worldwide to manage dyslipidaemia and thus limit the development of atherosclerotic disease and its complications. These atheroprotective drugs are now known to exert pleiotropic actions outside of their cholesterol-lowering activity, including altering immune cell function. Macrophages are phagocytic leukocytes that play critical functional roles in the pathogenesis of atherosclerosis and are directly targeted by statins. Early studies documented the anti-inflammatory effects of statins on macrophages, but emerging evidence suggests that these drugs can also enhance pro-inflammatory macrophage responses, creating an unresolved paradox. This review comprehensively examines the in vitro, in vivo, and clinical literature to document the statin-induced changes in macrophage polarization and immunomodulatory functions, explore the underlying mechanisms involved, and offer potential explanations for this paradox. A better understanding of the immunomodulatory actions of statins on macrophages should pave the way for the development of novel therapeutic approaches to manage atherosclerosis and other chronic diseases and conditions characterised by unresolved inflammation.https://www.mdpi.com/2673-5601/2/2/21statinsmacrophagesatherosclerosisinflammationcholesterolatorvastatin
spellingShingle Alanah Sheridan
Caroline P. D. Wheeler-Jones
Matthew C. Gage
The Immunomodulatory Effects of Statins on Macrophages
Immuno
statins
macrophages
atherosclerosis
inflammation
cholesterol
atorvastatin
title The Immunomodulatory Effects of Statins on Macrophages
title_full The Immunomodulatory Effects of Statins on Macrophages
title_fullStr The Immunomodulatory Effects of Statins on Macrophages
title_full_unstemmed The Immunomodulatory Effects of Statins on Macrophages
title_short The Immunomodulatory Effects of Statins on Macrophages
title_sort immunomodulatory effects of statins on macrophages
topic statins
macrophages
atherosclerosis
inflammation
cholesterol
atorvastatin
url https://www.mdpi.com/2673-5601/2/2/21
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