Abstract 12111: 17β-estradiol Suppresses Foam Cell Formation in a Suppressor of Cytokine Signaling 3 Dependent Manner
Background 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 macrophage foam cell formation in vivo and in vitro.
Methods and Results ApoE null mice underwent an ovariectomy (OVX) or sham operation at 5th week of age and then the OVX mice were treated with E2 or vehicle for the following 8 weeks. Compared with the vehicle treated mice, the serum total cholesterol level, triglyceride 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 the up-regulation was also achieved in RAW264.7 cells via estrogen receptor α. In vitro, janus kinase / signal transducers and activators of transcription (JAK/STAT) negatively regulated ABCA1 expression. E2 treatment reversed JAK/STAT-inhibited ABCA1 expression in RAW264.7 cells but the effect was abolished when knocking down SOCS3 by siRNA. SOCS3 over-expression elevated ABCA1 through the inhibition of JAK2/STAT3 phosphorylation. Finally, we also found that E2 enhanced the cholesterol efflux to apoA I and reduced lipid deposit and foam cell formation in RAW264.7 cells.
Conclusions In summary, E2 reduces atherosclerosis in ApoE null mice associated with up-regulating ABCA1 expression and modulating the cholesterol efflux, which are dependent on SOCS3 up-regulation. These results provide new insight into the athero-protective effects of estrogen.
- © 2012 by American Heart Association, Inc.