Calenduloside e modulates macrophage polarization via KLF2-regulated glycolysis, contributing to attenuates atherosclerosis.

Lanfang Li, Junyu Mou, Yanwei Han, Min Wang, Shan Lu, Qiuxiao Ma, Jialu Wang, Jingxue Ye, Guibo Sun

International immunopharmacology 2023 Apr

filter terms:

Glycolysis-mediated macrophage polarization plays a crucial role in atherosclerosis. Although it is known that calenduloside E (CE) exerts anti-inflammatory and lipid-lowering effects in atherosclerosis, the underlying mechanism of action is not clearly understood. We hypothesized that CE functions by inhibiting M1 macrophage polarization via regulation of glycolysis. To verify this hypothesis, we determined the effects of CE in apolipoprotein E deficient (ApoE-/-) mice and on macrophage polarization in oxidized low-density lipoprotein (ox-LDL)-induced RAW 264.7 macrophages and peritoneal macrophages. We also determined whether these effects are linked to regulation of glycolysis both in vivo and in vitro. The plaque size was reduced, and serum cytokine levels were decreased in the ApoE-/- +CE group compared with that in the model group. CE decreased lipid droplet formation, inflammatory factor levels, and mRNA levels of M1 macrophage markers in ox-ldl-induced macrophages. CE suppressed ox-ldl-induced glycolysis, lactate levels, and glucose uptake. The relationship between glycolysis and M1 macrophage polarization was demonstrated using the glycolysis inhibitor 3-(3-pyridinyl)-1-(4-pyridinyl)-2-propen-1-one. CE substantially upregulated ox-ldl-induced Kruppel-like transcription factor (KLF2) expression, and the effects of CE on ox-ldl-induced glycolysis and inflammatory factor levels disappeared after KLF2 knockdown. Together, our findings suggest that CE alleviates atherosclerosis by inhibiting glycolysis-mediated M1 macrophage polarization through upregulation of KLF2 expression, providing a new strategy for the treatment of atherosclerosis. Copyright © 2023. Published by Elsevier B.V.

Citation

Lanfang Li, Junyu Mou, Yanwei Han, Min Wang, Shan Lu, Qiuxiao Ma, Jialu Wang, Jingxue Ye, Guibo Sun. Calenduloside e modulates macrophage polarization via KLF2-regulated glycolysis, contributing to attenuates atherosclerosis. International immunopharmacology. 2023 Apr;117:109730