Lee Chien-Hsing, Su Sheng-Chiang, Chiang Chi-Fu, Chien Chu-Yen, Hsu Chia-Chen, Yu Tzu-Yi, Huang Shih-Ming, Shieh Yi-Shing, Kao Hong-Wei, Tsai Chien-Sung, Hung Yi-Jen, Lin Chih-Yuan
Division of Endocrinology and Metabolism, Department of Internal Medicine, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan.
Graduate Institute of Medical Sciences, National Defense Medical Center, Taipei, Taiwan.
Oncotarget. 2017 Nov 10;8(66):110039-110051. doi: 10.18632/oncotarget.22546. eCollection 2017 Dec 15.
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.
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, , and measured the expression of SIRT1 and apoptotic markers, as well as proliferation, viability, and migration.
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. , 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.
Estrogen may regulate cardiovascular health via the expression of SIRT1, possibly through the AKT and ERK signaling pathways.
心血管疾病的发病率和严重程度存在性别差异。尽管雌激素介导的血管保护作用已被广泛接受，但临床试验结果一直存在矛盾，具体机制仍不清楚。沉默调节蛋白1（SIRT1）是一种III类组蛋白去乙酰化酶，可能预防血管衰老和动脉粥样硬化；然而，雌激素对SIRT1表达和血管平滑肌细胞（VSMC）行为的影响尚不清楚。
我们对雌性野生型C57BL/6J小鼠进行卵巢切除（OVX），并将其随机分为非雌激素补充组和雌激素补充组。我们还用17-β-雌二醇和SIRT1激活剂白藜芦醇处理A7r5血管平滑肌细胞，并测量SIRT1和凋亡标志物的表达，以及增殖、活力和迁移情况。
通过蛋白质印迹法和免疫组织化学染色评估，OVX小鼠的主动脉组织表现出明显的血管平滑肌细胞增生和SIRT1上调，而补充17-β-雌二醇可使其逆转。17-β-雌二醇以剂量和时间依赖性方式下调SIRT1表达，增加细胞凋亡，并降低增殖、活力和迁移能力。白藜芦醇通过激活SIRT1逆转了这些作用。雌激素似乎通过Akt和ERK途径介导其作用。
雌激素可能通过SIRT1的表达调节心血管健康，可能是通过AKT和ERK信号通路。
