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Shexiang Tongxin Dropping Pills Promote Macrophage Polarization-Induced Angiogenesis Against Coronary Microvascular Dysfunction via PI3K/Akt/mTORC1 Pathway

Background: Accumulating evidence suggests that coronary microvascular dysfunction (CMD) is one of the important causes of coronary artery diseases. Angiogenesis can effectively improve CMD by increasing blood supply capacity, recovering cardiac function and poor hemodynamics. Clinical studies have...

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Autores principales: Lu, Xiangyu, Yao, Junkai, Li, Changxiang, Cui, Lingwen, Liu, Yizhou, Liu, Xiangning, Wang, Gang, Dong, Jianteng, Deng, Qiong, Hu, Yueyao, Guo, Dongqing, Wang, Wei, Li, Chun
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8984141/
https://www.ncbi.nlm.nih.gov/pubmed/35401214
http://dx.doi.org/10.3389/fphar.2022.840521
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author Lu, Xiangyu
Yao, Junkai
Li, Changxiang
Cui, Lingwen
Liu, Yizhou
Liu, Xiangning
Wang, Gang
Dong, Jianteng
Deng, Qiong
Hu, Yueyao
Guo, Dongqing
Wang, Wei
Li, Chun
author_facet Lu, Xiangyu
Yao, Junkai
Li, Changxiang
Cui, Lingwen
Liu, Yizhou
Liu, Xiangning
Wang, Gang
Dong, Jianteng
Deng, Qiong
Hu, Yueyao
Guo, Dongqing
Wang, Wei
Li, Chun
author_sort Lu, Xiangyu
collection PubMed
description Background: Accumulating evidence suggests that coronary microvascular dysfunction (CMD) is one of the important causes of coronary artery diseases. Angiogenesis can effectively improve CMD by increasing blood supply capacity, recovering cardiac function and poor hemodynamics. Clinical studies have approved Shexiang Tongxin dropping pill (STDP), which has exerted remarkable roles on ameliorating CMD, but the effects and mechanisms of STDPs on angiogenesis have not been clarified. Purpose: The purpose of this study was to elucidate the effects and potential mechanisms of STDPs on macrophage polarization-induced angiogenesis against CMD. Methods: Echocardiography, optical microangiography (OMAG), and histological examination were applied to evaluate cardioprotection and proangiogenic effects of STDPs on left anterior descending (LAD) ligation-induced CMD rats. In vitro, oxygen–glucose deprivation–reperfusion (OGD/R)-induced HUVEC model and LPS-stimulated bone marrow-derived macrophage (BMDM) model were established to observe the effects of STDPs on angiogenesis and M2 macrophage polarization. Results: STDPs improved cardiac function, increased microvascular density, and the number of M2 macrophages in the heart of CMD rats. In vitro, STDPs accelerated the proliferation, migration, and tube formation in OGD/R-induced HUVECs similar to the effects of VEGF-A. Furthermore, in LPS-stimulated BMDMs model, STDPs modulated M2 macrophage polarization and increased VEGF-A release via the PI3K/AKT/mTORC1 pathway. Conclusion: STDPs promoted macrophage polarization-induced angiogenesis against CMD via the PI3K/Akt/mTORC1 pathway. Our results demonstrated that the phenotype transformation of macrophages and stimulating the secretion of VEGF-A may be applied as novel cardioprotective targets for the treatment of CMD.
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spelling pubmed-89841412022-04-07 Shexiang Tongxin Dropping Pills Promote Macrophage Polarization-Induced Angiogenesis Against Coronary Microvascular Dysfunction via PI3K/Akt/mTORC1 Pathway Lu, Xiangyu Yao, Junkai Li, Changxiang Cui, Lingwen Liu, Yizhou Liu, Xiangning Wang, Gang Dong, Jianteng Deng, Qiong Hu, Yueyao Guo, Dongqing Wang, Wei Li, Chun Front Pharmacol Pharmacology Background: Accumulating evidence suggests that coronary microvascular dysfunction (CMD) is one of the important causes of coronary artery diseases. Angiogenesis can effectively improve CMD by increasing blood supply capacity, recovering cardiac function and poor hemodynamics. Clinical studies have approved Shexiang Tongxin dropping pill (STDP), which has exerted remarkable roles on ameliorating CMD, but the effects and mechanisms of STDPs on angiogenesis have not been clarified. Purpose: The purpose of this study was to elucidate the effects and potential mechanisms of STDPs on macrophage polarization-induced angiogenesis against CMD. Methods: Echocardiography, optical microangiography (OMAG), and histological examination were applied to evaluate cardioprotection and proangiogenic effects of STDPs on left anterior descending (LAD) ligation-induced CMD rats. In vitro, oxygen–glucose deprivation–reperfusion (OGD/R)-induced HUVEC model and LPS-stimulated bone marrow-derived macrophage (BMDM) model were established to observe the effects of STDPs on angiogenesis and M2 macrophage polarization. Results: STDPs improved cardiac function, increased microvascular density, and the number of M2 macrophages in the heart of CMD rats. In vitro, STDPs accelerated the proliferation, migration, and tube formation in OGD/R-induced HUVECs similar to the effects of VEGF-A. Furthermore, in LPS-stimulated BMDMs model, STDPs modulated M2 macrophage polarization and increased VEGF-A release via the PI3K/AKT/mTORC1 pathway. Conclusion: STDPs promoted macrophage polarization-induced angiogenesis against CMD via the PI3K/Akt/mTORC1 pathway. Our results demonstrated that the phenotype transformation of macrophages and stimulating the secretion of VEGF-A may be applied as novel cardioprotective targets for the treatment of CMD. Frontiers Media S.A. 2022-03-23 /pmc/articles/PMC8984141/ /pubmed/35401214 http://dx.doi.org/10.3389/fphar.2022.840521 Text en Copyright © 2022 Lu, Yao, Li, Cui, Liu, Liu, Wang, Dong, Deng, Hu, Guo, Wang and Li. 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
Lu, Xiangyu
Yao, Junkai
Li, Changxiang
Cui, Lingwen
Liu, Yizhou
Liu, Xiangning
Wang, Gang
Dong, Jianteng
Deng, Qiong
Hu, Yueyao
Guo, Dongqing
Wang, Wei
Li, Chun
Shexiang Tongxin Dropping Pills Promote Macrophage Polarization-Induced Angiogenesis Against Coronary Microvascular Dysfunction via PI3K/Akt/mTORC1 Pathway
title Shexiang Tongxin Dropping Pills Promote Macrophage Polarization-Induced Angiogenesis Against Coronary Microvascular Dysfunction via PI3K/Akt/mTORC1 Pathway
title_full Shexiang Tongxin Dropping Pills Promote Macrophage Polarization-Induced Angiogenesis Against Coronary Microvascular Dysfunction via PI3K/Akt/mTORC1 Pathway
title_fullStr Shexiang Tongxin Dropping Pills Promote Macrophage Polarization-Induced Angiogenesis Against Coronary Microvascular Dysfunction via PI3K/Akt/mTORC1 Pathway
title_full_unstemmed Shexiang Tongxin Dropping Pills Promote Macrophage Polarization-Induced Angiogenesis Against Coronary Microvascular Dysfunction via PI3K/Akt/mTORC1 Pathway
title_short Shexiang Tongxin Dropping Pills Promote Macrophage Polarization-Induced Angiogenesis Against Coronary Microvascular Dysfunction via PI3K/Akt/mTORC1 Pathway
title_sort shexiang tongxin dropping pills promote macrophage polarization-induced angiogenesis against coronary microvascular dysfunction via pi3k/akt/mtorc1 pathway
topic Pharmacology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8984141/
https://www.ncbi.nlm.nih.gov/pubmed/35401214
http://dx.doi.org/10.3389/fphar.2022.840521
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