Estrogen modulates vascular smooth muscle cell function through downregulation of SIRT1.
Estrogen modulates vascular smooth muscle cell function through downregulation of SIRT1.
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DOI：
10.18632/oncotarget.22546
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发表时间：
2017-12-15
期刊：
影响因子：
--
通讯作者：
Lin CY
中科院分区：
文献类型：
--
作者：
Lee CH;Su SC;Chiang CF;Chien CY;Hsu CC;Yu TY;Huang SM;Shieh YS;Kao HW;Tsai CS;Hung YJ;Lin CY
心血管疾病的发病率和严重程度存在性别差异。虽然雌激素介导的血管保护作用被广泛接受，但临床试验结果一直相互矛盾，详细的机制仍不清楚。Sirtuin 1（SIRT 1）是一种III类组蛋白去乙酰化酶，可保护血管老化和动脉粥样硬化;然而，雌激素对SIRT 1表达和血管平滑肌细胞（VSMC）行为的影响尚不清楚。我们切除卵巢（OVX）雌性，野生型，C57 BL/6 J小鼠，随机分为非雌激素和雌激素补充组。我们还在体外用17-β-雌二醇和白藜芦醇（一种SIRT 1激活剂）处理A7 r5 VSMCs，并测量SIRT 1和凋亡标记物的表达，以及增殖、活力和迁移。通过免疫印迹和免疫组织化学染色评估，OVX小鼠的主动脉组织显示出显著的VSMC增生和SIRT 1上调，补充17-β-雌二醇可逆转这一点。在体外，17-β-雌二醇以剂量和时间依赖性方式下调SIRT 1表达，增加凋亡，减少增殖、活力和迁移。白藜芦醇通过激活SIRT 1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SIRT 1的表达调节心血管健康，可能通过AKT和ERK信号通路。
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, in vitro, 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. 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. Estrogen may regulate cardiovascular health via the expression of SIRT1, possibly through the AKT and ERK signaling pathways.
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影响因子：
82.9
作者：
Iafrati, MD;Karas, RH;Mendelsohn, ME
通讯作者：
Mendelsohn, ME
影响因子：
2.7
作者：
Hisamoto, K;Bender, JR
通讯作者：
Bender, JR
影响因子：
3.4
作者：
Mathur, Pankaj;Ostadal, Bohuslav;Mehta, Jawahar L.
通讯作者：
Mehta, Jawahar L.
DOI：
10.1007/978-1-62703-637-5_1
发表时间：
2013-01-01
期刊：
SIRTUINS: METHODS AND PROTOCOLS
影响因子：
--
作者：
Guarente, Leonard
通讯作者：
Guarente, Leonard
影响因子：
64.8
作者：
Finkel T;Deng CX;Mostoslavsky R
通讯作者：
Mostoslavsky R