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Traditional Chinese Medication Tongxinluo Attenuates Lipidosis in Ox-LDL-Stimulated Macrophages by Enhancing Beclin-1-Induced Autophagy

Tongxinluo (TXL), a traditional Chinese medication, plays a key role in the formation and progression of plaques in atherosclerosis. The formation of foam cells by macrophages accelerates the destabilisation of plaques. In previous research, we had found that TXL significantly inhibits ox-LDL-induce...

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Autores principales: Chen, Yifei, Yu, Fangpu, Zhang, Yu, Li, Mengmeng, Di, Mingxue, Chen, Weijia, Liu, Xiaolin, Zhang, Yun, Zhang, Mei
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8267176/
https://www.ncbi.nlm.nih.gov/pubmed/34248627
http://dx.doi.org/10.3389/fphar.2021.673366
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author Chen, Yifei
Yu, Fangpu
Zhang, Yu
Li, Mengmeng
Di, Mingxue
Chen, Weijia
Liu, Xiaolin
Zhang, Yun
Zhang, Mei
author_facet Chen, Yifei
Yu, Fangpu
Zhang, Yu
Li, Mengmeng
Di, Mingxue
Chen, Weijia
Liu, Xiaolin
Zhang, Yun
Zhang, Mei
author_sort Chen, Yifei
collection PubMed
description Tongxinluo (TXL), a traditional Chinese medication, plays a key role in the formation and progression of plaques in atherosclerosis. The formation of foam cells by macrophages accelerates the destabilisation of plaques. In previous research, we had found that TXL significantly inhibits ox-LDL-induced apoptosis in macrophages in vitro by improving the dissociation of the Beclin-1-Bcl-2 complex. Therefore, here, we explored the effect of TXL on lipid metabolism in macrophages and the mechanism involved. To evaluate the role of TXL in atherosclerotic plaques, we construct the atherosclerotic animal model with lentiviral injection and performed immunofluorescence staining analysis in vivo. Western blot, immunofluorescence staining and microscopy were performed to elucidate the mechanism underlying TXL-mediated regulation of autophagy in THP-1 macrophages in vitro. Immunofluorescence assay revealed that TXL treatment inhibited lipid deposition in advanced atherosclerotic plaques. In vitro TXL treatment inhibited lipid deposition in THP-1 macrophages by enhancing autophagy via Beclin-1. TXL reversed the high expression of class I histone deacetylases (HDACs) induced by ox-LDL (p < 0.05). Compared with the TXL + ox-LDL group, TXL failed to promote intracellular lipid droplet decomposition after the addition of the histone deacetylase agonist. We found that TXL attenuates the accumulation of lipids in macrophage by enhancing Beclin-1-induced autophagy, and additionally, it inhibits the inhibitory effect of class I HDAC on the expression of Beclin-1.
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spelling pubmed-82671762021-07-10 Traditional Chinese Medication Tongxinluo Attenuates Lipidosis in Ox-LDL-Stimulated Macrophages by Enhancing Beclin-1-Induced Autophagy Chen, Yifei Yu, Fangpu Zhang, Yu Li, Mengmeng Di, Mingxue Chen, Weijia Liu, Xiaolin Zhang, Yun Zhang, Mei Front Pharmacol Pharmacology Tongxinluo (TXL), a traditional Chinese medication, plays a key role in the formation and progression of plaques in atherosclerosis. The formation of foam cells by macrophages accelerates the destabilisation of plaques. In previous research, we had found that TXL significantly inhibits ox-LDL-induced apoptosis in macrophages in vitro by improving the dissociation of the Beclin-1-Bcl-2 complex. Therefore, here, we explored the effect of TXL on lipid metabolism in macrophages and the mechanism involved. To evaluate the role of TXL in atherosclerotic plaques, we construct the atherosclerotic animal model with lentiviral injection and performed immunofluorescence staining analysis in vivo. Western blot, immunofluorescence staining and microscopy were performed to elucidate the mechanism underlying TXL-mediated regulation of autophagy in THP-1 macrophages in vitro. Immunofluorescence assay revealed that TXL treatment inhibited lipid deposition in advanced atherosclerotic plaques. In vitro TXL treatment inhibited lipid deposition in THP-1 macrophages by enhancing autophagy via Beclin-1. TXL reversed the high expression of class I histone deacetylases (HDACs) induced by ox-LDL (p < 0.05). Compared with the TXL + ox-LDL group, TXL failed to promote intracellular lipid droplet decomposition after the addition of the histone deacetylase agonist. We found that TXL attenuates the accumulation of lipids in macrophage by enhancing Beclin-1-induced autophagy, and additionally, it inhibits the inhibitory effect of class I HDAC on the expression of Beclin-1. Frontiers Media S.A. 2021-06-25 /pmc/articles/PMC8267176/ /pubmed/34248627 http://dx.doi.org/10.3389/fphar.2021.673366 Text en Copyright © 2021 Chen, Yu, Zhang, Li, Di, Chen, Liu, Zhang and Zhang. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Pharmacology
Chen, Yifei
Yu, Fangpu
Zhang, Yu
Li, Mengmeng
Di, Mingxue
Chen, Weijia
Liu, Xiaolin
Zhang, Yun
Zhang, Mei
Traditional Chinese Medication Tongxinluo Attenuates Lipidosis in Ox-LDL-Stimulated Macrophages by Enhancing Beclin-1-Induced Autophagy
title Traditional Chinese Medication Tongxinluo Attenuates Lipidosis in Ox-LDL-Stimulated Macrophages by Enhancing Beclin-1-Induced Autophagy
title_full Traditional Chinese Medication Tongxinluo Attenuates Lipidosis in Ox-LDL-Stimulated Macrophages by Enhancing Beclin-1-Induced Autophagy
title_fullStr Traditional Chinese Medication Tongxinluo Attenuates Lipidosis in Ox-LDL-Stimulated Macrophages by Enhancing Beclin-1-Induced Autophagy
title_full_unstemmed Traditional Chinese Medication Tongxinluo Attenuates Lipidosis in Ox-LDL-Stimulated Macrophages by Enhancing Beclin-1-Induced Autophagy
title_short Traditional Chinese Medication Tongxinluo Attenuates Lipidosis in Ox-LDL-Stimulated Macrophages by Enhancing Beclin-1-Induced Autophagy
title_sort traditional chinese medication tongxinluo attenuates lipidosis in ox-ldl-stimulated macrophages by enhancing beclin-1-induced autophagy
topic Pharmacology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8267176/
https://www.ncbi.nlm.nih.gov/pubmed/34248627
http://dx.doi.org/10.3389/fphar.2021.673366
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