Oncotarget

Research Papers:

Estrogen modulates vascular smooth muscle cell function through downregulation of SIRT1

Chien-Hsing Lee, Sheng-Chiang Su, Chi-Fu Chiang, Chu-Yen Chien, Chia-Chen Hsu, Tzu-Yi Yu, Shih-Ming Huang, Yi-Shing Shieh, Hong-Wei Kao, Chien-Sung Tsai, Yi-Jen Hung and Chih-Yuan Lin _

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Oncotarget. 2017; 8:110039-110051. https://doi.org/10.18632/oncotarget.22546

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Abstract

Chien-Hsing Lee1, Sheng-Chiang Su1, Chi-Fu Chiang2, Chu-Yen Chien2, Chia-Chen Hsu2, Tzu-Yi Yu3, Shih-Ming Huang3, Yi-Shing Shieh4, Hong-Wei Kao5, Chien-Sung Tsai6, Yi-Jen Hung1 and Chih-Yuan Lin6

1Division of Endocrinology and Metabolism, Department of Internal Medicine, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan

2Graduate Institute of Medical Sciences, National Defense Medical Center, Taipei, Taiwan

3Department of Biochemistry, National Defense Medical Center, Taipei, Taiwan

4Department of Oral Diagnosis and Pathology, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan

5Department of Pathology, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan

6Division of Cardiovascular Surgery, Department of Surgery, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan

Correspondence to:

Chih-Yuan Lin, email: linrock@ms26.hinet.net

Keywords: estrogen; sirtuin 1 (SIRT1); vascular smooth muscle cell; ovariectomy

Received: September 13, 2017     Accepted: October 27, 2017     Published: November 10, 2017

ABSTRACT

Background: There are sex differences in the incidence and severity of cardiovascular disease. Although an estrogen-mediated vasculoprotective effect is widely accepted, clinical trial results have been conflicting and the detailed mechanisms are still unclear. Sirtuin 1 (SIRT1), a class III histone deacetylase, may protect against vascular aging and atherosclerosis; however, the effects of estrogen on SIRT1 expression and vascular smooth muscle cell (VSMC) behavior remain unknown.

Materials and Methods: We ovariectomized (OVX) female, wild-type, C57BL/6J mice, which were randomized into non-estrogen- and estrogen-supplemented groups. We also treated A7r5 VSMCs with 17-β-estradiol and resveratrol, a SIRT1 activator, in vitro, and measured the expression of SIRT1 and apoptotic markers, as well as proliferation, viability, and migration.

Results: Aortic tissue from OVX mice exhibited marked VSMC hyperplasia and upregulation of SIRT1, which was reversed by 17-β-estradiol supplementation, as assessed by western blotting and immunohistochemical staining. In vitro, 17-β-estradiol downregulated SIRT1 expression in a dose- and time-dependent manner, increased apoptosis, and reduced proliferation, viability, and migration. Resveratrol reversed these effects through the activation of SIRT1. Estrogen appeared to mediate its effects through the Akt and ERK pathways.

Conclusions: Estrogen may regulate cardiovascular health via the expression of SIRT1, possibly through the AKT and ERK signaling pathways.


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