2,3,5,4′-tetrahydroxystilbene-2-O-β-D-glucoside ameliorates vascular senescence and improves blood flow involving a mechanism of p53 deacetylation
2,3,5,4′-tetrahydroxystilbene-2-O-β-D-glucoside ameliorates vascular senescence and improves blood flow involving a mechanism of p53 deacetylation
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DOI：
10.1016/j.atherosclerosis.2012.08.011
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发表时间：
2012-11-01
期刊：
影响因子：
5.3
通讯作者：
Xu, Jin-Wen
中科院分区：
文献类型：
--
作者：
Han, Xin;Ling, Shuang;Xu, Jin-Wen
背景和目标：2，3，5，4 '-四羟基二苯乙烯-2-O-β-D-葡萄糖苷（THSG）是一种具有葡萄糖苷的白藜芦醇类似物，在各种研究中已显示出抑制血管平滑肌细胞增殖、减轻炎症和预防血管内皮功能障碍。方法和结果：口服THSG 14周，可显著增加自发性高血压大鼠（SHR）的血流量;并有效抑制血管衰老，如衰老相关的β-半乳糖苷酶所示（SA-β-gal）染色，通过免疫荧光染色分析观察到的γ H2 AX的磷酸化，以及SHR主动脉弓中p53的K373乙酰化。口服THSG还诱导eNOS表达和尿NOx产生。THSG每周激活SIRT 1活性，刺激eNOS启动子报告基因活性，并改善H2 O2诱导的细胞衰老和K373乙酰化p53。THSG至少部分通过增加eNOS表达和Sirt 1活性以及减少K373位点p53的乙酰化来改善血流并改善血管衰老，无论是在体外还是在体内。(C)2012爱思唯尔爱尔兰有限公司保留所有权利。
Background and aims: 2,3,5,4'-tetrahydroxystilbene-2-O-beta-D-glucoside (THSG), a resveratrol analog with glucoside, has been shown in various studies to inhibit proliferation of vascular smooth muscle cells, attenuate inflammation, and prevent vascular endothelial dysfunction. In the study, we examined the effects of THSG on vascular senescence and blood flow.Methods and results: Oral administration of THSG for 14 weeks, resulted in notable increases in blood flow in spontaneously hypertensive rats (SHRs); and effective inhibition of vascular senescence as indicated by senescence-associated beta-galactosidase (SA-beta-gal) staining, phosphorylation of gamma H2AX observed by stain analysis of immunofluorescence, and K373 acetylation of p53 in the aortic arches of SHRs. Oral administration of THSG also induced eNOS expression and urinary NOx production. THSG weekly activated SIRT1 activity, stimulated eNOS promoter reporter gene activity, and ameliorated H2O2-induced cellular senescence and K373 acetylation of p53 in cultured human umbilical vein endothelial cells (HUVECs).Conclusions: THSG improves blood flow and ameliorates vascular senescence by increasing eNOS expression and Sirt1 activity and decreasing acetylation of p53 at K373 site, at least in part, both in vitro and in vivo. (C) 2012 Elsevier Ireland Ltd. All rights reserved.