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Anti-Atherosclerotic Effect of Gossypetin on Abnormal Vascular Smooth Muscle Cell Proliferation and Migration

Gossypetin (GTIN), known as 3,5,7,8,3′,4′-hexahydroxyflavone, has been demonstrated to exert anti-atherosclerotic potential against apoptotic injury in oxidized low-density lipoprotein-incubated endothelial cells, and atherosclerotic lesions of cholesterol-fed rabbits. However, the effect and underl...

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Autores principales: Lin, Hui-Hsuan, Hsieh, Ming-Chang, Wang, Chi-Ping, Yu, Pei-Rong, Lee, Ming-Shih, Chen, Jing-Hsien
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8470489/
https://www.ncbi.nlm.nih.gov/pubmed/34572989
http://dx.doi.org/10.3390/antiox10091357
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author Lin, Hui-Hsuan
Hsieh, Ming-Chang
Wang, Chi-Ping
Yu, Pei-Rong
Lee, Ming-Shih
Chen, Jing-Hsien
author_facet Lin, Hui-Hsuan
Hsieh, Ming-Chang
Wang, Chi-Ping
Yu, Pei-Rong
Lee, Ming-Shih
Chen, Jing-Hsien
author_sort Lin, Hui-Hsuan
collection PubMed
description Gossypetin (GTIN), known as 3,5,7,8,3′,4′-hexahydroxyflavone, has been demonstrated to exert anti-atherosclerotic potential against apoptotic injury in oxidized low-density lipoprotein-incubated endothelial cells, and atherosclerotic lesions of cholesterol-fed rabbits. However, the effect and underlying mechanism of GTIN on abnormal vascular smooth muscle cells (VSMCs) proliferation and migration, a major event in the pathogenesis of atherosclerosis, is still unknown. In this study, non-cytotoxic doses of GTIN abolished the VSMCs A7r5 proliferation and cell-cycle S phase distribution. The GTIN-arrested G0/G1 phase might be performed by increasing the expressions of phosphorylated p53 and its downstream molecules that inhibit the activation of cyclin E/cyclin-dependent kinase (cdk)-2, blocking retinoblastoma protein (Rb) phosphorylation and the subsequent dissociation of Rb/transcription factor E2F1 complex. In addition, the results indicated that GTIN inhibited VSMCs wound-healing and migratory abilities through reducing matrix metalloproteinase (MMP)-9 activity and expression, as well as down-regulating protein kinase B (PKB)/nuclear factor-kappaB (NF-κB) signaling. GTIN also revealed potential in diminishing reactive oxygen species (ROS) generation. These findings suggested the inhibitory effects of GTIN on VSMCs dysfunction could likely lead to the containment of atherosclerosis and other cardiovascular illness.
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spelling pubmed-84704892021-09-27 Anti-Atherosclerotic Effect of Gossypetin on Abnormal Vascular Smooth Muscle Cell Proliferation and Migration Lin, Hui-Hsuan Hsieh, Ming-Chang Wang, Chi-Ping Yu, Pei-Rong Lee, Ming-Shih Chen, Jing-Hsien Antioxidants (Basel) Article Gossypetin (GTIN), known as 3,5,7,8,3′,4′-hexahydroxyflavone, has been demonstrated to exert anti-atherosclerotic potential against apoptotic injury in oxidized low-density lipoprotein-incubated endothelial cells, and atherosclerotic lesions of cholesterol-fed rabbits. However, the effect and underlying mechanism of GTIN on abnormal vascular smooth muscle cells (VSMCs) proliferation and migration, a major event in the pathogenesis of atherosclerosis, is still unknown. In this study, non-cytotoxic doses of GTIN abolished the VSMCs A7r5 proliferation and cell-cycle S phase distribution. The GTIN-arrested G0/G1 phase might be performed by increasing the expressions of phosphorylated p53 and its downstream molecules that inhibit the activation of cyclin E/cyclin-dependent kinase (cdk)-2, blocking retinoblastoma protein (Rb) phosphorylation and the subsequent dissociation of Rb/transcription factor E2F1 complex. In addition, the results indicated that GTIN inhibited VSMCs wound-healing and migratory abilities through reducing matrix metalloproteinase (MMP)-9 activity and expression, as well as down-regulating protein kinase B (PKB)/nuclear factor-kappaB (NF-κB) signaling. GTIN also revealed potential in diminishing reactive oxygen species (ROS) generation. These findings suggested the inhibitory effects of GTIN on VSMCs dysfunction could likely lead to the containment of atherosclerosis and other cardiovascular illness. MDPI 2021-08-26 /pmc/articles/PMC8470489/ /pubmed/34572989 http://dx.doi.org/10.3390/antiox10091357 Text en © 2021 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Lin, Hui-Hsuan
Hsieh, Ming-Chang
Wang, Chi-Ping
Yu, Pei-Rong
Lee, Ming-Shih
Chen, Jing-Hsien
Anti-Atherosclerotic Effect of Gossypetin on Abnormal Vascular Smooth Muscle Cell Proliferation and Migration
title Anti-Atherosclerotic Effect of Gossypetin on Abnormal Vascular Smooth Muscle Cell Proliferation and Migration
title_full Anti-Atherosclerotic Effect of Gossypetin on Abnormal Vascular Smooth Muscle Cell Proliferation and Migration
title_fullStr Anti-Atherosclerotic Effect of Gossypetin on Abnormal Vascular Smooth Muscle Cell Proliferation and Migration
title_full_unstemmed Anti-Atherosclerotic Effect of Gossypetin on Abnormal Vascular Smooth Muscle Cell Proliferation and Migration
title_short Anti-Atherosclerotic Effect of Gossypetin on Abnormal Vascular Smooth Muscle Cell Proliferation and Migration
title_sort anti-atherosclerotic effect of gossypetin on abnormal vascular smooth muscle cell proliferation and migration
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8470489/
https://www.ncbi.nlm.nih.gov/pubmed/34572989
http://dx.doi.org/10.3390/antiox10091357
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