國家衛生研究院 NHRI:Item 3990099045/13553
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    题名: Punicalagin attenuates disturbed flow-induced vascular dysfunction by inhibiting force-specific activation of smad1/5
    作者: Anwaier, G;Lian, G;Ma, GZ;Shen, WL;Lee, CI;Lee, PL;Chang, ZY;Wang, YX;Tian, XY;Gao, XL;Chiu, JJ;Qi, R
    贡献者: Institute of Cellular and Systems Medicine
    摘要: Background Pathophysiological vascular remodeling in response to disturbed flow with low and oscillatory shear stress (OSS) plays important roles in atherosclerosis progression. Pomegranate extraction (PE) was reported having anti-atherogenic effects. However, whether it can exert a beneficial effect against disturbed flow-induced pathophysiological vascular remodeling to inhibit atherosclerosis remains unclear. The present study aims at investigating the anti-atherogenic effects of pomegranate peel polyphenols (PPP) extraction and its purified compound punicalagin (PU), as well as their protective effects on disturbed flow-induced vascular dysfunction and their underlying molecular mechanisms. Methods The anti-atherogenic effects of PPP/PU were examined on low-density lipoprotein receptor knockout mice fed with a high fat diet. The vaso-protective effects of PPP/PU were examined in rat aortas using myograph assay. A combination of in vivo experiments on rats and in vitro flow system with human endothelial cells (ECs) was used to investigate the pharmacological actions of PPP/PU on EC dysfunction induced by disturbed flow. In addition, the effects of PPP/PU on vascular smooth muscle cell (VSMC) dysfunction were also examined. Results PU is the effective component in PPP against atherosclerosis. PPP/PU evoked endothelium-dependent relaxation in rat aortas. PPP/PU inhibited the activation of Smad1/5 in the EC layers at post-stenotic regions of rat aortas exposed to disturbed flow with OSS. PPP/PU suppressed OSS-induced expression of cell cycle regulatory and pro-inflammatory genes in ECs. Moreover, PPP/PU inhibited inflammation-induced VSMC dysfunction. Conclusion PPP/PU protect against OSS-induced vascular remodeling through inhibiting force-specific activation of Smad1/5 in ECs and this mechanism contributes to their anti-atherogenic effects.
    日期: 2021-06-28
    關聯: Frontiers in Cell and Developmental Biology. 2021 Jun 28;9:Article number 697539.
    Link to: http://dx.doi.org/10.3389/fcell.2021.697539
    JIF/Ranking 2023: http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=NHRI&SrcApp=NHRI_IR&KeyISSN=2296-634X&DestApp=IC2JCR
    Cited Times(WOS): https://www.webofscience.com/wos/woscc/full-record/WOS:000671826900001
    Cited Times(Scopus): https://www.scopus.com/inward/record.url?partnerID=HzOxMe3b&scp=85110005582
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