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Article

17β-estradiol promotes cholesterol efflux from vascular smooth muscle cells through a liver X receptor α-dependent pathway

  • Authors:
    • Huan Wang
    • Yan Liu
    • Ling Zhu
    • Wenjing Wang
    • Zhaofei Wan
    • Fangyuan Chen
    • Yan Wu
    • Juan Zhou
    • Zuyi Yuan
  • View Affiliations / Copyright

    Affiliations: Department of Cardiovascular Medicine, The First Affiliated Hospital of the Medical School, Xi'an Jiaotong University, Xi'an, Shaanxi 710061, P.R. China
  • Pages: 550-558
    |
    Published online on: January 8, 2014
       https://doi.org/10.3892/ijmm.2014.1619
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Abstract

Estrogen has pleiotropic effects on the cardiovascular diseases, yet the underlying mechanisms remain incompletely understood. Cholesterol efflux is a key mechanism through which to prevent foam cell formation and the development of atherosclerosis. Recent studies highlight the role of vascular smooth muscle cell (VSMC)-derived foam cells in atherogenesis. However, it remains unclear whether estrogen promotes cholesterol efflux from VSMCs and inhibits VSMC-derived foam cell formation. In the present study, we demonstrated that 17β-estradiol (E2) markedly enhanced cholesterol efflux to apolipoprotein (apo)A-1 and high-density lipoprotein (HDL) and attenuated oxidized low-density lipoprotein (ox-LDL) induced cholesteryl ester accumulation in VSMCs, which was associated with an increase in the expression of ATP-binding cassette transporters ABCA1 and ABCG1. The upregulation of ABCA1 and ABCG1 expression by E2 resulted from liver X receptor (LXR)α activation, which was confirmed by the prevention of the expression of ABCA1 and ABCG1 after inhibition of LXRα with a pharmacological inhibitor or small interfering RNA (siRNA). Furthermore, E2 increased LXRα, ABCA1 and ABCG1 expression in VSMCs via the estrogen receptor (ER), and the involvement of ERβ was confirmed by the use of selective ERα or ERβ antagonists (MPP and PHTPP) and agonists (PPT and DPN). These findings suggest that E2 promotes cholesterol efflux from VSMCs and reduces VSMC-derived foam cell formation via ERβ- and LXRα-dependent upregulation of ABCA1 and ABCG1 and provide novel insights into the anti-atherogenic properties of estrogen.
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Copy and paste a formatted citation
Spandidos Publications style
Wang H, Liu Y, Zhu L, Wang W, Wan Z, Chen F, Wu Y, Zhou J and Yuan Z: 17β-estradiol promotes cholesterol efflux from vascular smooth muscle cells through a liver X receptor α-dependent pathway. Int J Mol Med 33: 550-558, 2014.
APA
Wang, H., Liu, Y., Zhu, L., Wang, W., Wan, Z., Chen, F. ... Yuan, Z. (2014). 17β-estradiol promotes cholesterol efflux from vascular smooth muscle cells through a liver X receptor α-dependent pathway. International Journal of Molecular Medicine, 33, 550-558. https://doi.org/10.3892/ijmm.2014.1619
MLA
Wang, H., Liu, Y., Zhu, L., Wang, W., Wan, Z., Chen, F., Wu, Y., Zhou, J., Yuan, Z."17β-estradiol promotes cholesterol efflux from vascular smooth muscle cells through a liver X receptor α-dependent pathway". International Journal of Molecular Medicine 33.3 (2014): 550-558.
Chicago
Wang, H., Liu, Y., Zhu, L., Wang, W., Wan, Z., Chen, F., Wu, Y., Zhou, J., Yuan, Z."17β-estradiol promotes cholesterol efflux from vascular smooth muscle cells through a liver X receptor α-dependent pathway". International Journal of Molecular Medicine 33, no. 3 (2014): 550-558. https://doi.org/10.3892/ijmm.2014.1619
Copy and paste a formatted citation
x
Spandidos Publications style
Wang H, Liu Y, Zhu L, Wang W, Wan Z, Chen F, Wu Y, Zhou J and Yuan Z: 17β-estradiol promotes cholesterol efflux from vascular smooth muscle cells through a liver X receptor α-dependent pathway. Int J Mol Med 33: 550-558, 2014.
APA
Wang, H., Liu, Y., Zhu, L., Wang, W., Wan, Z., Chen, F. ... Yuan, Z. (2014). 17β-estradiol promotes cholesterol efflux from vascular smooth muscle cells through a liver X receptor α-dependent pathway. International Journal of Molecular Medicine, 33, 550-558. https://doi.org/10.3892/ijmm.2014.1619
MLA
Wang, H., Liu, Y., Zhu, L., Wang, W., Wan, Z., Chen, F., Wu, Y., Zhou, J., Yuan, Z."17β-estradiol promotes cholesterol efflux from vascular smooth muscle cells through a liver X receptor α-dependent pathway". International Journal of Molecular Medicine 33.3 (2014): 550-558.
Chicago
Wang, H., Liu, Y., Zhu, L., Wang, W., Wan, Z., Chen, F., Wu, Y., Zhou, J., Yuan, Z."17β-estradiol promotes cholesterol efflux from vascular smooth muscle cells through a liver X receptor α-dependent pathway". International Journal of Molecular Medicine 33, no. 3 (2014): 550-558. https://doi.org/10.3892/ijmm.2014.1619
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