Please use this identifier to cite or link to this item:
doi:10.22028/D291-35052
Title: | Statins and Bempedoic Acid: Different Actions of Cholesterol Inhibitors on Macrophage Activation |
Author(s): | Linnenberger, Rebecca Hoppstädter, Jessica Wrublewsky, Selina Ampofo, Emmanuel Kiemer, Alexandra K. |
Language: | English |
Title: | International Journal of Molecular Sciences |
Volume: | 22 |
Issue: | 22 |
Publisher/Platform: | MDPI |
Year of Publication: | 2021 |
Free key words: | natural compounds polarization bone marrow-derived macrophages LPS phagocytosis arginase HMG-CoA reductase inflammasome GILZ KLF2 |
DDC notations: | 500 Science 610 Medicine and health |
Publikation type: | Journal Article |
Abstract: | Statins represent the most prescribed class of drugs for the treatment of hypercholes terolemia. 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 mat ter 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., simvas tatin and cerivastatin, impaired phagocytotic activity and, concurrently, enhanced pro-inflammatory responses upon short-term lipopolysaccharide challenge, as characterized by an induction of tu mor 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. |
DOI of the first publication: | 10.3390/ijms222212480 |
Link to this record: | urn:nbn:de:bsz:291--ds-350528 hdl:20.500.11880/32132 http://dx.doi.org/10.22028/D291-35052 |
ISSN: | 1422-0067 |
Date of registration: | 5-Jan-2022 |
Description of the related object: | Supplementary Material |
Related object: | https://www.mdpi.com/1422-0067/22/22/12480/s1 |
Faculty: | M - Medizinische Fakultät NT - Naturwissenschaftlich- Technische Fakultät |
Department: | M - Chirurgie NT - Pharmazie |
Professorship: | M - Prof. Dr. Michael D. Menger NT - Prof. Dr. Alexandra K. Kiemer |
Collections: | SciDok - Der Wissenschaftsserver der Universität des Saarlandes |
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ijms-22-12480.pdf | 4,1 MB | Adobe PDF | View/Open |
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