17β-estradiol suppresses the macrophage foam cell formation associated with SOCS3.

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.

• Authors: X Liang, M He, T Chen, Y Wu, Y Tian, Y Zhao, Y Shen, Y Liu, Z Yuan
• Journal: Hormone and metabolic research = Hormon- und Stoffwechselforschung = Hormones et metabolisme (Horm Metab Res) Vol. 45 Issue 6 Pg. 423-9 (Jun 2013) ISSN: 1439-4286 [Electronic] Germany
• PMID: 23430591 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © Georg Thieme Verlag KG Stuttgart · New York.

Chemical References

• ABCA1 protein, mouse
• ATP Binding Cassette Transporter 1
• STAT3 Transcription Factor
• Socs3 protein, mouse
• Suppressor of Cytokine Signaling 3 Protein
• Suppressor of Cytokine Signaling Proteins
• Estradiol
• Cholesterol
• Janus Kinase 2

Topics

• ATP Binding Cassette Transporter 1 (genetics, metabolism)
• Animals
• Atherosclerosis (genetics, metabolism)
• Cells, Cultured
• Cholesterol (metabolism)
• Down-Regulation
• Estradiol (metabolism)
• Female
• Foam Cells (metabolism)
• Humans
• Janus Kinase 2 (genetics, metabolism)
• Male
• Mice
• Mice, Knockout
• Phosphorylation
• STAT3 Transcription Factor (genetics, metabolism)
• Signal Transduction
• Suppressor of Cytokine Signaling 3 Protein
• Suppressor of Cytokine Signaling Proteins (genetics, metabolism)
• Up-Regulation