Statins and Bempedoic Acid: Different Actions of Cholesterol Inhibitors on Macrophage Activation

Statins represent the most prescribed class of drugs for the treatment of hypercholesterolemia. Effects that go beyond lipid-lowering actions have been suggested to contribute to their beneficial pharmacological properties. Whether and how statins act on macrophages has been a matter of debate. In t...

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Autores principales:	Rebecca Linnenberger, Jessica Hoppstädter, Selina Wrublewsky, Emmanuel Ampofo, Alexandra K. Kiemer
Formato:	article
Lenguaje:	EN
Publicado:	MDPI AG 2021
Materias:	natural compounds polarization bone marrow-derived macrophages LPS phagocytosis arginase Biology (General) QH301-705.5 Chemistry QD1-999
Acceso en línea:	https://doaj.org/article/adda120468d44cabaca055c16a408a5f
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spelling	oai:doaj.org-article:adda120468d44cabaca055c16a408a5f2021-11-25T17:57:04ZStatins and Bempedoic Acid: Different Actions of Cholesterol Inhibitors on Macrophage Activation10.3390/ijms2222124801422-00671661-6596https://doaj.org/article/adda120468d44cabaca055c16a408a5f2021-11-01T00:00:00Zhttps://www.mdpi.com/1422-0067/22/22/12480https://doaj.org/toc/1661-6596https://doaj.org/toc/1422-0067Statins represent the most prescribed class of drugs for the treatment of hypercholesterolemia. Effects that go beyond lipid-lowering actions have been suggested to contribute to their beneficial pharmacological properties. Whether and how statins act on macrophages has been a matter of debate. In the present study, we aimed at characterizing the impact of statins on macrophage polarization and comparing these to the effects of bempedoic acid, a recently registered drug for the treatment of hypercholesterolemia, which has been suggested to have a similar beneficial profile but fewer side effects. Treatment of primary murine macrophages with two different statins, i.e., simvastatin and cerivastatin, impaired phagocytotic activity and, concurrently, enhanced pro-inflammatory responses upon short-term lipopolysaccharide challenge, as characterized by an induction of tumor necrosis factor (TNF), interleukin (IL) 1β, and IL6. In contrast, no differences were observed under long-term inflammatory (M1) or anti-inflammatory (M2) conditions, and neither inducible NO synthase (iNOS) expression nor nitric oxide production was altered. Statin treatment led to extracellular-signal regulated kinase (ERK) activation, and the pro-inflammatory statin effects were abolished by ERK inhibition. Bempedoic acid only had a negligible impact on macrophage responses when compared with statins. Taken together, our data point toward an immunomodulatory effect of statins on macrophage polarization, which is absent upon bempedoic acid treatment.Rebecca LinnenbergerJessica HoppstädterSelina WrublewskyEmmanuel AmpofoAlexandra K. KiemerMDPI AGarticlenatural compoundspolarizationbone marrow-derived macrophagesLPSphagocytosisarginaseBiology (General)QH301-705.5ChemistryQD1-999ENInternational Journal of Molecular Sciences, Vol 22, Iss 12480, p 12480 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	natural compounds polarization bone marrow-derived macrophages LPS phagocytosis arginase Biology (General) QH301-705.5 Chemistry QD1-999
spellingShingle	natural compounds polarization bone marrow-derived macrophages LPS phagocytosis arginase Biology (General) QH301-705.5 Chemistry QD1-999 Rebecca Linnenberger Jessica Hoppstädter Selina Wrublewsky Emmanuel Ampofo Alexandra K. Kiemer Statins and Bempedoic Acid: Different Actions of Cholesterol Inhibitors on Macrophage Activation
description	Statins represent the most prescribed class of drugs for the treatment of hypercholesterolemia. Effects that go beyond lipid-lowering actions have been suggested to contribute to their beneficial pharmacological properties. Whether and how statins act on macrophages has been a matter of debate. In the present study, we aimed at characterizing the impact of statins on macrophage polarization and comparing these to the effects of bempedoic acid, a recently registered drug for the treatment of hypercholesterolemia, which has been suggested to have a similar beneficial profile but fewer side effects. Treatment of primary murine macrophages with two different statins, i.e., simvastatin and cerivastatin, impaired phagocytotic activity and, concurrently, enhanced pro-inflammatory responses upon short-term lipopolysaccharide challenge, as characterized by an induction of tumor necrosis factor (TNF), interleukin (IL) 1β, and IL6. In contrast, no differences were observed under long-term inflammatory (M1) or anti-inflammatory (M2) conditions, and neither inducible NO synthase (iNOS) expression nor nitric oxide production was altered. Statin treatment led to extracellular-signal regulated kinase (ERK) activation, and the pro-inflammatory statin effects were abolished by ERK inhibition. Bempedoic acid only had a negligible impact on macrophage responses when compared with statins. Taken together, our data point toward an immunomodulatory effect of statins on macrophage polarization, which is absent upon bempedoic acid treatment.
format	article
author	Rebecca Linnenberger Jessica Hoppstädter Selina Wrublewsky Emmanuel Ampofo Alexandra K. Kiemer
author_facet	Rebecca Linnenberger Jessica Hoppstädter Selina Wrublewsky Emmanuel Ampofo Alexandra K. Kiemer
author_sort	Rebecca Linnenberger
title	Statins and Bempedoic Acid: Different Actions of Cholesterol Inhibitors on Macrophage Activation
title_short	Statins and Bempedoic Acid: Different Actions of Cholesterol Inhibitors on Macrophage Activation
title_full	Statins and Bempedoic Acid: Different Actions of Cholesterol Inhibitors on Macrophage Activation
title_fullStr	Statins and Bempedoic Acid: Different Actions of Cholesterol Inhibitors on Macrophage Activation
title_full_unstemmed	Statins and Bempedoic Acid: Different Actions of Cholesterol Inhibitors on Macrophage Activation
title_sort	statins and bempedoic acid: different actions of cholesterol inhibitors on macrophage activation
publisher	MDPI AG
publishDate	2021
url	https://doaj.org/article/adda120468d44cabaca055c16a408a5f
work_keys_str_mv	AT rebeccalinnenberger statinsandbempedoicaciddifferentactionsofcholesterolinhibitorsonmacrophageactivation AT jessicahoppstadter statinsandbempedoicaciddifferentactionsofcholesterolinhibitorsonmacrophageactivation AT selinawrublewsky statinsandbempedoicaciddifferentactionsofcholesterolinhibitorsonmacrophageactivation AT emmanuelampofo statinsandbempedoicaciddifferentactionsofcholesterolinhibitorsonmacrophageactivation AT alexandrakkiemer statinsandbempedoicaciddifferentactionsofcholesterolinhibitorsonmacrophageactivation
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Statins and Bempedoic Acid: Different Actions of Cholesterol Inhibitors on Macrophage Activation

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