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

International Journal of Molecular Sciences

Rebecca Linnenberger¹  Alexandra K. Kiemer¹  Jessica Hoppstädter¹  Selina Wrublewsky²  Emmanuel Ampofo² 

[1] Department of Pharmacy, Pharmaceutical Biology, Saarland University, Campus C2.3, 66123 Saarbrücken, Germany;Institute of Clinical and Experimental Surgery, Saarland University, 66424 Homburg, Germany;

关键词: natural compounds;    polarization;    bone marrow-derived macrophages;    LPS;    phagocytosis;    arginase;   

DOI  :  10.3390/ijms222212480

来源: DOAJ

【 摘 要 】

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.

【 授权许可】

Unknown