Frontiers in Cell and Developmental Biology (Jun 2021)
Punicalagin Attenuates Disturbed Flow-Induced Vascular Dysfunction by Inhibiting Force-Specific Activation of Smad1/5
- 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
Affiliations
- Gulinigaer Anwaier
- Department of Pharmacology, School of Basic Medical Sciences, Peking University Health Science Center, Beijing, China
- Gulinigaer Anwaier
- Key Laboratory of Molecular Cardiovascular Sciences, Ministry of Education, Peking University, Beijing, China
- Gulinigaer Anwaier
- State Key Laboratory of Natural and Biomimetic Drugs, Peking University, Beijing, China
- Gulinigaer Anwaier
- National Health Commission (NHC) Key Laboratory of Cardiovascular Molecular Biology and Regulatory Peptides, Peking University, Beijing, China
- Gulinigaer Anwaier
- Beijing Key Laboratory of Molecular Pharmaceutics and New Drug Delivery Systems, Peking University, Beijing, China
- Guan Lian
- Department of Pharmacology, School of Basic Medical Sciences, Peking University Health Science Center, Beijing, China
- Guan Lian
- Key Laboratory of Molecular Cardiovascular Sciences, Ministry of Education, Peking University, Beijing, China
- Guan Lian
- State Key Laboratory of Natural and Biomimetic Drugs, Peking University, Beijing, China
- Guan Lian
- National Health Commission (NHC) Key Laboratory of Cardiovascular Molecular Biology and Regulatory Peptides, Peking University, Beijing, China
- Guan Lian
- Beijing Key Laboratory of Molecular Pharmaceutics and New Drug Delivery Systems, Peking University, Beijing, China
- Gui-Zhi Ma
- College of Pharmacy, Xinjiang Medical University, Xinjiang, China
- Gui-Zhi Ma
- Xinjiang Key Laboratory of Active Components and Drug Release Technology of Natural Drugs, Xinjiang, China
- Wan-Li Shen
- Department of Pharmacology, School of Basic Medical Sciences, Peking University Health Science Center, Beijing, China
- Wan-Li Shen
- Key Laboratory of Molecular Cardiovascular Sciences, Ministry of Education, Peking University, Beijing, China
- Wan-Li Shen
- State Key Laboratory of Natural and Biomimetic Drugs, Peking University, Beijing, China
- Wan-Li Shen
- National Health Commission (NHC) Key Laboratory of Cardiovascular Molecular Biology and Regulatory Peptides, Peking University, Beijing, China
- Wan-Li Shen
- Beijing Key Laboratory of Molecular Pharmaceutics and New Drug Delivery Systems, Peking University, Beijing, China
- Chih-I Lee
- 0Institute of Cellular and System Medicine, National Health Research Institutes, Miaoli, Taiwan
- Pei-Ling Lee
- 0Institute of Cellular and System Medicine, National Health Research Institutes, Miaoli, Taiwan
- Zhan-Ying Chang
- College of Pharmacy, Xinjiang Medical University, Xinjiang, China
- Zhan-Ying Chang
- Xinjiang Key Laboratory of Active Components and Drug Release Technology of Natural Drugs, Xinjiang, China
- Yun-Xia Wang
- Department of Pharmacology, School of Basic Medical Sciences, Peking University Health Science Center, Beijing, China
- Yun-Xia Wang
- Key Laboratory of Molecular Cardiovascular Sciences, Ministry of Education, Peking University, Beijing, China
- Yun-Xia Wang
- State Key Laboratory of Natural and Biomimetic Drugs, Peking University, Beijing, China
- Yun-Xia Wang
- National Health Commission (NHC) Key Laboratory of Cardiovascular Molecular Biology and Regulatory Peptides, Peking University, Beijing, China
- Yun-Xia Wang
- Beijing Key Laboratory of Molecular Pharmaceutics and New Drug Delivery Systems, Peking University, Beijing, China
- Xiao-Yu Tian
- 3School of Biomedical Sciences, Chinese University of Hong Kong, Hong Kong, China
- Xiao-Li Gao
- College of Pharmacy, Xinjiang Medical University, Xinjiang, China
- Xiao-Li Gao
- Xinjiang Key Laboratory of Active Components and Drug Release Technology of Natural Drugs, Xinjiang, China
- Jeng-Jiann Chiu
- School of Medical Laboratory Science and Biotechnology, College of Medical Science and Technology, Taipei Medical University, Taipei, Taiwan
- Jeng-Jiann Chiu
- Taipei Heart Institute, Taipei Medical University, Taipei, Taiwan
- Jeng-Jiann Chiu
- 0Institute of Cellular and System Medicine, National Health Research Institutes, Miaoli, Taiwan
- Jeng-Jiann Chiu
- 1Institute of Biomedical Engineering, National Tsing Hua University, Hsinchu, Taiwan
- Jeng-Jiann Chiu
- 2Institute of Polymer Science and Engineering, National Taiwan University, Taipei, Taiwan
- Rong Qi
- Department of Pharmacology, School of Basic Medical Sciences, Peking University Health Science Center, Beijing, China
- Rong Qi
- Key Laboratory of Molecular Cardiovascular Sciences, Ministry of Education, Peking University, Beijing, China
- Rong Qi
- State Key Laboratory of Natural and Biomimetic Drugs, Peking University, Beijing, China
- Rong Qi
- National Health Commission (NHC) Key Laboratory of Cardiovascular Molecular Biology and Regulatory Peptides, Peking University, Beijing, China
- Rong Qi
- Beijing Key Laboratory of Molecular Pharmaceutics and New Drug Delivery Systems, Peking University, Beijing, China
- DOI
- https://doi.org/10.3389/fcell.2021.697539
- Journal volume & issue
-
Vol. 9
Abstract
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.
Keywords
