Key result
FXR agonist GW4064 reduces atherosclerotic plaque and foam cell formation in ApoE-deficient mice.
Why the study?
Does FXR activation with GW4064 reduce foam cell formation and atherosclerotic plaque in preclinical models?
Does FXR activation with GW4064 reduce foam cell formation and atherosclerotic plaque in preclinical models?
Answers are grounded in this paper and cite their sources.
FXR activation with GW4064 exerts anti-atherosclerotic effects by reducing macrophage foam cell formation and plaque development, potentially via downregulation of hepatic lipase.
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.
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Gu et al. (2024) studied Atherosclerosis. FXR agonist GW4064 was evaluated on Atherosclerotic plaque formation, foam cell formation, and lipid levels. FXR agonist GW4064 decreased hepatic lipase expression, foam cell formation, and alleviated atherosclerotic plaque formation in ApoE -/- mice.
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