Estrogen modulates vascular smooth muscle cell function through downregulation of SIRT1

雌激素通过下调 SIRT1 来调节血管平滑肌细胞功能

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作者: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, Chih-Yuan Lin

Background

There are sex differences in the incidence and severity of cardiovascular disease. Although an estrogen-mediated vasculoprotective effect is widely accepted, clinical trial

Conclusions

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

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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