Punicalagin Attenuates Disturbed Flow-Induced Vascular Dysfunction by Inhibiting Force-Specific Activation of Smad1/5.
Punicalagin Attenuates Disturbed Flow-Induced Vascular Dysfunction by Inhibiting Force-Specific Activation of Smad1/5.
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安石榴苷通过抑制 Smad1/5 的力特异性激活来减轻血流紊乱引起的血管功能障碍
DOI：
10.3389/fcell.2021.697539
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发表时间：
2021
影响因子：
5.5
通讯作者：
Qi R
中科院分区：
文献类型：
--
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
背景低剪应力和振荡剪应力（OSS）干扰血流的病理生理性血管重构在动脉粥样硬化的进展中起重要作用。据报道，石榴提取物（PE）具有抗动脉粥样硬化作用。然而，它是否能对血流紊乱引起的病理生理血管重构起到有益的抑制动脉粥样硬化的作用尚不清楚。本研究旨在探讨石榴皮多酚（PPP）提取物及其纯化化合物punicalagin （PU）的抗动脉粥样硬化作用、对血流紊乱引起的血管功能障碍的保护作用及其分子机制。方法采用高脂饲料喂养低密度脂蛋白受体敲除小鼠，观察PPP/PU的抗动脉粥样硬化作用。采用肌图法观察PPP/PU对大鼠主动脉的血管保护作用。采用大鼠体内实验和体外内皮细胞流动系统相结合的方法，研究了PPP/PU对血流紊乱所致内皮细胞功能障碍的药理作用。此外，我们还观察了PPP/PU对血管平滑肌细胞功能障碍的影响。结果PU是PPP抗动脉粥样硬化的有效成分。PPP/PU诱导大鼠主动脉内皮依赖性松弛。PPP/PU可抑制OSS干扰血流的大鼠主动脉狭窄后区EC层Smad1/5的激活。PPP/PU抑制oss诱导的ECs细胞周期调控基因和促炎基因的表达。此外，PPP/PU抑制炎症诱导的VSMC功能障碍。结论PPP/PU通过抑制ECs中Smad1/5的力特异性激活，对oss诱导的血管重构具有保护作用，这一机制与PPP/PU的抗动脉粥样硬化作用有关。
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.
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影响因子：
--
作者：
Atrahimovich D;Samson AO;Khattib A;Vaya J;Khatib S
通讯作者：
Khatib S
影响因子：
--
作者：
Atrahimovich D;Khatib S;Sela S;Vaya J;Samson AO
通讯作者：
Samson AO
影响因子：
20.1
作者：
Gimbrone MA Jr;García-Cardeña G
通讯作者：
García-Cardeña G
影响因子：
3.7
作者：
Go YM;Son DJ;Park H;Orr M;Hao L;Takabe W;Kumar S;Kang DW;Kim CW;Jo H;Jones DP
通讯作者：
Jones DP
DOI：
10.1161/01.atv.0000106321.63667.24
发表时间：
2004-01-01
影响因子：
8.7
作者：
Chiu, JJ;Lee, PL;Chien, S
通讯作者：
Chien, S