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Titel: Statins and Bempedoic Acid: Different Actions of Cholesterol Inhibitors on Macrophage Activation
VerfasserIn: Linnenberger, Rebecca
Hoppstädter, Jessica
Wrublewsky, Selina
Ampofo, Emmanuel
Kiemer, Alexandra K.
Sprache: Englisch
Titel: International Journal of Molecular Sciences
Bandnummer: 22
Heft: 22
Verlag/Plattform: MDPI
Erscheinungsjahr: 2021
Freie Schlagwörter: natural compounds
polarization
bone marrow-derived macrophages
LPS
phagocytosis
arginase
HMG-CoA reductase
inflammasome
GILZ
KLF2
DDC-Sachgruppe: 500 Naturwissenschaften
610 Medizin, Gesundheit
Dokumenttyp: Journalartikel / Zeitschriftenartikel
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 der Erstveröffentlichung: 10.3390/ijms222212480
Link zu diesem Datensatz: urn:nbn:de:bsz:291--ds-350528
hdl:20.500.11880/32132
http://dx.doi.org/10.22028/D291-35052
ISSN: 1422-0067
Datum des Eintrags: 5-Jan-2022
Bezeichnung des in Beziehung stehenden Objekts: Supplementary Material
In Beziehung stehendes Objekt: https://www.mdpi.com/1422-0067/22/22/12480/s1
Fakultät: M - Medizinische Fakultät
NT - Naturwissenschaftlich- Technische Fakultät
Fachrichtung: M - Chirurgie
NT - Pharmazie
Professur: M - Prof. Dr. Michael D. Menger
NT - Prof. Dr. Alexandra K. Kiemer
Sammlung:SciDok - Der Wissenschaftsserver der Universität des Saarlandes

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