Related Experiment Video
Updated: May 14, 2026
Culture of Macrophage Colony-stimulating Factor Differentiated Human Monocyte-derived Macrophages
Published on: June 30, 2016
17β-estradiol suppresses the macrophage foam cell formation associated with SOCS3
1Department of Cardiovascular Medicine, First Affiliated Hospital of Medical School, Xi'an Jiaotong University, Xi'an, Shaanxi, P. R. China.
Abstract:
Evidence from clinical trials and animal experiments has shown that estrogen has anti-atherosclerotic effects when administered to young women or experimental animals. The mechanisms involve the modulation of vascular inflammation, growth factor expression, and oxidative stress injured arteries. However, whether estrogen modulates the foam cell formation in plaque remains unknown. Here, we investigated the effects of 17β-estradiol (E2) on cholesterol efflux in vivo and in vitro. ApoE null mice underwent an ovariectomy at 5(th) week of age and then were treated with E2 or vehicle for the following 8 weeks. Compared with the vehicle-treated mice, the serum total cholesterol level, atherosclerotic plaque size, and lipid deposits were decreased and meanwhile ATP-binding cassette transporter A1 (ABCA1) expression in the plaque was increased in mice with E2 treatment. E2 also increased suppressor of cytokine signaling 3 (SOCS3) expression in the atherosclerotic plaques and in RAW264.7 cells. In vitro, E2 treatment reversed janus kinase/signal transducers and activators of transcription (JAK/STAT)-inhibited ABCA1 expression in RAW264.7 cells but had no effect on ABCA1 expression in SOCS3 knockdown cells. SOCS3 overexpression elevated ABCA1 expression through the inhibition of JAK2/STAT3 phosphorylation. Finally, we also found that E2 enhanced the cholesterol efflux to apoA I in RAW264.7 cells. In summary, E2 reduces atherosclerosis in ApoE null mice associated with upregulating ABCA1 expression and modulating the cholesterol efflux, which are dependent on SOCS3 upregulation. These results provide new insight into the athero-protective effects of estrogen.
Insights
Estrogen (17β-estradiol) reduces atherosclerosis by increasing cholesterol efflux via ATP-binding cassette transporter A1 (ABCA1) upregulation, a process dependent on suppressor of cytokine signaling 3 (SOCS3). This finding offers new insights into estrogen's athero-protective effects.
Area of Science:
- Endocrinology
- Cardiovascular Biology
- Molecular Medicine
Background:
- Estrogen exhibits anti-atherosclerotic effects, modulating vascular inflammation and oxidative stress.
- The precise mechanisms by which estrogen influences foam cell formation and cholesterol efflux in atherosclerosis remain incompletely understood.
Purpose of the Study:
- To investigate the effects of 17β-estradiol (E2) on cholesterol efflux and foam cell formation in vivo and in vitro.
- To elucidate the role of suppressor of cytokine signaling 3 (SOCS3) and ATP-binding cassette transporter A1 (ABCA1) in mediating E2's athero-protective actions.
Main Methods:
- ApoE null mice underwent ovariectomy and were treated with E2 or vehicle.
- Assessment of serum cholesterol, plaque size, lipid deposits, and ABCA1/SOCS3 expression in atherosclerotic plaques.
- In vitro studies using RAW264.7 cells to examine E2's effects on ABCA1 expression, cholesterol efflux, and the JAK/STAT signaling pathway.
Main Results:
- E2 treatment significantly decreased serum total cholesterol, atherosclerotic plaque size, and lipid deposits in ApoE null mice.
- E2 upregulated ABCA1 and SOCS3 expression in atherosclerotic plaques and RAW264.7 cells.
- In vitro, E2 reversed JAK/STAT-inhibited ABCA1 expression, enhanced cholesterol efflux to apoA I, and these effects were SOCS3-dependent.
Conclusions:
- 17β-estradiol reduces atherosclerosis in ApoE null mice by upregulating ABCA1 expression and enhancing cholesterol efflux.
- The athero-protective effects of E2 are mediated through SOCS3 upregulation, which modulates ABCA1 expression and cholesterol homeostasis.
- These findings provide novel insights into the molecular mechanisms underlying estrogen's role in preventing atherosclerosis.
