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Punicalagin Attenuates Disturbed Flow-Induced Vascular Dysfunction by Inhibiting Force-Specific Activation of Smad1/5
oleh: Gulinigaer Anwaier, Gulinigaer Anwaier, Gulinigaer Anwaier, Gulinigaer Anwaier, Gulinigaer Anwaier, Guan Lian, Guan Lian, Guan Lian, Guan Lian, Guan Lian, Gui-Zhi Ma, Gui-Zhi Ma, Wan-Li Shen, Wan-Li Shen, Wan-Li Shen, Wan-Li Shen, Wan-Li Shen, Chih-I Lee, Pei-Ling Lee, Zhan-Ying Chang, Zhan-Ying Chang, Yun-Xia Wang, Yun-Xia Wang, Yun-Xia Wang, Yun-Xia Wang, Yun-Xia Wang, Xiao-Yu Tian, Xiao-Li Gao, Xiao-Li Gao, Jeng-Jiann Chiu, Jeng-Jiann Chiu, Jeng-Jiann Chiu, Jeng-Jiann Chiu, Jeng-Jiann Chiu, Rong Qi, Rong Qi, Rong Qi, Rong Qi, Rong Qi
Format: | Article |
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Diterbitkan: | Frontiers Media S.A. 2021-06-01 |
Deskripsi
BackgroundPathophysiological 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.MethodsThe 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.ResultsPU 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.ConclusionPPP/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.