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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: Linnenberger, Rebecca, Hoppstädter, Jessica, Wrublewsky, Selina, Ampofo, Emmanuel, Kiemer, Alexandra K.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8623589/
https://www.ncbi.nlm.nih.gov/pubmed/34830364
http://dx.doi.org/10.3390/ijms222212480
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author Linnenberger, Rebecca
Hoppstädter, Jessica
Wrublewsky, Selina
Ampofo, Emmanuel
Kiemer, Alexandra K.
author_facet Linnenberger, Rebecca
Hoppstädter, Jessica
Wrublewsky, Selina
Ampofo, Emmanuel
Kiemer, Alexandra K.
author_sort Linnenberger, Rebecca
collection PubMed
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.
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spelling pubmed-86235892021-11-27 Statins and Bempedoic Acid: Different Actions of Cholesterol Inhibitors on Macrophage Activation Linnenberger, Rebecca Hoppstädter, Jessica Wrublewsky, Selina Ampofo, Emmanuel Kiemer, Alexandra K. Int J Mol Sci Article 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. MDPI 2021-11-19 /pmc/articles/PMC8623589/ /pubmed/34830364 http://dx.doi.org/10.3390/ijms222212480 Text en © 2021 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Linnenberger, Rebecca
Hoppstädter, Jessica
Wrublewsky, Selina
Ampofo, Emmanuel
Kiemer, Alexandra K.
Statins and Bempedoic Acid: Different Actions of Cholesterol Inhibitors on Macrophage Activation
title 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_short 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
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8623589/
https://www.ncbi.nlm.nih.gov/pubmed/34830364
http://dx.doi.org/10.3390/ijms222212480
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