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 - Keiner Professur zugeordnet
NT - Prof. Dr. Alexandra K. Kiemer
Collections:SciDok - Der Wissenschaftsserver der Universität des Saarlandes

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