Work

FXR activation reduces the formation of macrophage foam cells and atherosclerotic plaque, possibly by down regulating hepatic lipase in macrophages

Year: 2024

Type: article

Abstract: Macrophages are the most important immune cells affecting the formation of atherosclerotic plaque. Nevertheless, the mechanisms that promote formation of foamy macrophages during atherogenesis remain poorly understood. This study explored the effects of Farnesoid X receptor (FXR) and hepatic lipase (HL, encoded by LIPC ) on atherogenesis, particularly in foamy macrophage formation. A luciferase reporter assay indicated that FXR could bind to the LIPC promoter and inhibit LIPC transcription. FXR agonist GW4064 decreased HL expression, foam cell formation, and increased the expression of FXR downstream genes and polarization to M2 in ox‐LDL‐induced THP‐1 and U937 foam cells. In addition, GW4064 exerted anti‐atherosclerotic effects in ApoE −/− mice, manifested as decreased serum cholesterol and triglyceride levels, and alleviated atherosclerotic plaque formation. Collectively, FXR exerted anti‐atherosclerotic effects, possibly by negatively regulating HL expression in macrophages.

Source: FEBS Open Bio

DOI: 10.1002/2211-5463.13925

Authors: Qiang Gu, Jia Liu, Li Li Shen

Institutions: Army Medical University, Xinqiao Hospital, Chongqing University, Chongqing Cancer Hospital

Language: English

Topic: Cholesterol and Lipid Metabolism

Subfield: Surgery

Field: Medicine

Domain: Health Sciences

SDG: Good health and well-being

Open Access status: gold

Estimated APC paid: $2,010