Identification of resveratrol derivative 3,3',4,4',5,5'-hexamethoxy- trans-stilbene as a novel pro-angiogenic small-molecule compound.

Identification of resveratrol derivative 3,3',4,4',5,5'-hexamethoxy- trans-stilbene as a novel pro-angiogenic small-molecule compound.
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DOI:
10.1016/j.ejphar.2016.08.034
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发表时间:
2016-11
影响因子:
5
通讯作者:
Zhou B
Zhou B
中科院分区:
医学2区
文献类型:
--
作者:
Chen Z;ZHANG L;Yu J;Chen L;Zhou B

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The potential to promote neovascularization in ischemic tissues using exogenous agents is an attractive avenue for therapeutics. To identify novel pro-angiogenic small-molecule compound, we screened a series of resveratrol methylated derivatives and identified 3,3′,4,4′, 5,5′-hexamethoxy-trans-stilbene (3,3′,4,4′,5,5′-HMS) potently promotes proliferation, migration, invasion and tube formation of human umbilical vein VECs (HUVECs)in vitro. Furthermore, 3,3′,4,4′,5,5′-HMS accelerates neo-vessels sprouting of rat aortic ringsex vivo, and neovascularization of chick chorioallantoic membrane (CAM) and mouse matrigel plugsin vivo. Microarray analyses show that the level of early growth response 1 (EGR-1), an inducible pro-angiogenic gene regulatory factor, was upregulated. The upregulation of EGR-1 was confirmed by semiquantitative RT-PCR, quantitative real-time PCR and western blotting analyses. In addition, the levels of several pro-angiogenic factors including transforming growth factor β1 (TGF-β1), vascular endothelial growth factor (VEGF), nitric oxide (NO), and the activity of endothelial NO synthase (eNOS) were elevated in 3,3′,4,4′,5,5′-HMS-treated HUVECs. Inhibition of NO synthase byl-NAME blocked the pro-angiogenic effects of 3,3′,4,4′,5,5′-HMS. Our research shows that 3,3′,4,4′,5,5′-HMS dramatically promoted angiogenesisin vitro, ex vivoandin vivo,which might represent a novel potential agent for the development of therapeutic drugs to treat ischemic diseases.
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