Punicalagin Attenuates Disturbed Flow-Induced Vascular Dysfunction by Inhibiting Force-Specific Activation of Smad1/5

Frontiers in Cell and Developmental Biology

卷:9

Pei-Ling Lee¹  Chih-I Lee¹  Jeng-Jiann Chiu³  Xiao-Yu Tian⁴  Gulinigaer Anwaier⁵  Guan Lian⁵  Rong Qi⁵  Yun-Xia Wang⁵  Wan-Li Shen⁵  Xiao-Li Gao¹³  Zhan-Ying Chang¹³  Gui-Zhi Ma¹³ 

[1] 0Institute of Cellular and System Medicine, National Health Research Institutes, Miaoli, Taiwan;

[2] 1Institute of Biomedical Engineering, National Tsing Hua University, Hsinchu, Taiwan;

[3] 2Institute of Polymer Science and Engineering, National Taiwan University, Taipei, Taiwan;

[4] 3School of Biomedical Sciences, Chinese University of Hong Kong, Hong Kong, China;

[5] Beijing Key Laboratory of Molecular Pharmaceutics and New Drug Delivery Systems, Peking University, Beijing, China;

[6] College of Pharmacy, Xinjiang Medical University, Xinjiang, China;

[7] Department of Pharmacology, School of Basic Medical Sciences, Peking University Health Science Center, Beijing, China;

[8] Key Laboratory of Molecular Cardiovascular Sciences, Ministry of Education, Peking University, Beijing, China;

[9] National Health Commission (NHC) Key Laboratory of Cardiovascular Molecular Biology and Regulatory Peptides, Peking University, Beijing, China;

[10] School of Medical Laboratory Science and Biotechnology, College of Medical Science and Technology, Taipei Medical University, Taipei, Taiwan;

[11] State Key Laboratory of Natural and Biomimetic Drugs, Peking University, Beijing, China;

[12] Taipei Heart Institute, Taipei Medical University, Taipei, Taiwan;

[13] Xinjiang Key Laboratory of Active Components and Drug Release Technology of Natural Drugs, Xinjiang, China;

关键词: pomegranate;    punicalagin;    oscillatory shear stress;    atherosclerosis;    endothelial cell;    Smads;   

DOI  :  10.3389/fcell.2021.697539

来源: DOAJ

【 摘 要 】

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.

【 授权许可】

Unknown