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Updated: Oct 27, 2025
Isolation, Characterization, and Purification of Macrophages from Tissues Affected by Obesity-related Inflammation
Published on: April 3, 2017
CTRP1 decreases ABCA1 expression and promotes lipid accumulation through the miR-424-5p/FoxO1 pathway in THP-1
Zi-Zhen Zhang1, Jiao-Jiao Chen2, Wen-Yi Deng2
1School of Medicine, Hunan Polytechnic of Environment and Biology, Hengyang, Hunan, China.
Abstract:
Prevention of ATP binding cassette transporter A1 (ABCA1)-dependent cholesterol efflux leads to lipid accumulation in macrophages and atherosclerosis development. C1q tumor necrosis factor-related protein 1 (CTRP1), a conserved paralog of adiponectin, has been shown to aggravate atherosclerosis via its proinflammatory property. However, very little is known about its effects on ABCA1 expression and macrophage lipid accumulation. In the current studies, we found that CTRP1 downregulated ABCA1 expression, inhibited cholesterol efflux to apoA-I and promoted lipid accumulation in THP-1 macrophage-derived foam cells. Forkhead box O1 (FoxO1), a transcriptional repressor of ABCA1, was identified as a direct target of miR-424-5p. Mechanistically, CTRP1 attenuated miR-424-5p levels and then augmented FoxO1 expression in the nucleus, which led to downregulation of ABCA1 expression and inhibition of cholesterol efflux. In conclusion, these findings suggest that CTRP1 restrains cholesterol efflux and facilitates macrophage lipid accumulation through the miR-424-5p/FoxO1/ABCA1 signaling pathway, thereby providing a novel mechanistical insight into its proatherosclerotic action.
Insights
C1q tumor necrosis factor-related protein 1 (CTRP1) worsens atherosclerosis by reducing cholesterol removal from macrophages. CTRP1 lowers ABCA1 transporter expression via a miR-424-5p/FoxO1 pathway, promoting foam cell formation.
Area of Science:
- Molecular Biology
- Cardiovascular Research
- Cell Biology
Background:
- ATP binding cassette transporter A1 (ABCA1) is crucial for cholesterol efflux from macrophages, and its dysfunction contributes to atherosclerosis.
- C1q tumor necrosis factor-related protein 1 (CTRP1), an adiponectin paralog, is implicated in promoting atherosclerosis through inflammation.
Purpose of the Study:
- To investigate the role of CTRP1 in regulating ABCA1 expression and macrophage lipid accumulation.
- To elucidate the molecular mechanisms underlying CTRP1's effects on cholesterol homeostasis.
Main Methods:
- Utilized THP-1 macrophage-derived foam cells to assess CTRP1's impact on ABCA1 expression and cholesterol efflux.
- Investigated the involvement of microRNA-424-5p (miR-424-5p) and Forkhead box O1 (FoxO1) in the CTRP1 signaling pathway.
Main Results:
- CTRP1 significantly downregulated ABCA1 expression and inhibited cholesterol efflux to apoA-I in macrophages.
- CTRP1 promoted lipid accumulation in macrophage-derived foam cells.
- CTRP1 was found to decrease miR-424-5p levels, leading to increased nuclear FoxO1 expression and subsequent ABCA1 downregulation.
Conclusions:
- CTRP1 restrains cholesterol efflux and promotes macrophage lipid accumulation by inhibiting the miR-424-5p/FoxO1/ABCA1 signaling pathway.
- These findings offer novel mechanistic insights into CTRP1's proatherosclerotic actions.
