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DanHong injection targets endothelin receptor type B and angiotensin II receptor type 1 in protection against cardiac hypertrophy

Cardiac hypertrophy (CH) is an independent risk factor for cardiovascular diseases (CVDs). Mitigating or preventing CH is the most effective strategy for the treatment of CVDs. DanHong injection (DH) is a Chinese herbal medicine preparation (CHMP) widely used in clinical treatment of several CVDs in...

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Autores principales: Zhang, Min-Yu, Guo, Fei-Fei, Wu, Hong-Wei, Yu, Yang-Yang, Wei, Jun-Ying, Wang, Shi-Feng, Zhang, Yu-Xin, Xian, Ming-Hua, Wu, Qing-Hua, Zhao, Bu-Chang, Li, Shi-You, Yang, Hong-Jun
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Impact Journals LLC 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5732736/
https://www.ncbi.nlm.nih.gov/pubmed/29262570
http://dx.doi.org/10.18632/oncotarget.21900
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author Zhang, Min-Yu
Guo, Fei-Fei
Wu, Hong-Wei
Yu, Yang-Yang
Wei, Jun-Ying
Wang, Shi-Feng
Zhang, Yu-Xin
Xian, Ming-Hua
Wu, Qing-Hua
Zhao, Bu-Chang
Li, Shi-You
Yang, Hong-Jun
author_facet Zhang, Min-Yu
Guo, Fei-Fei
Wu, Hong-Wei
Yu, Yang-Yang
Wei, Jun-Ying
Wang, Shi-Feng
Zhang, Yu-Xin
Xian, Ming-Hua
Wu, Qing-Hua
Zhao, Bu-Chang
Li, Shi-You
Yang, Hong-Jun
author_sort Zhang, Min-Yu
collection PubMed
description Cardiac hypertrophy (CH) is an independent risk factor for cardiovascular diseases (CVDs). Mitigating or preventing CH is the most effective strategy for the treatment of CVDs. DanHong injection (DH) is a Chinese herbal medicine preparation (CHMP) widely used in clinical treatment of several CVDs in China. However, the direct targets and cellular mechanisms for these protective effects remain unclear. This study was designed to illustrate the direct targets of DH in protecting against CH and investigate CH molecular pathogenesis. A hypertrophic cell model was induced by endothelin-1 (ET-1) on human induced pluripotent stem cell-derived cardiomyocytes (hiPS-CMs). Real time cellular analysis (RTCA) cardio system and high content analysis (HCA) were used to detect the changes in contractile function, morphology and protein level of hypertrophic hiPS-CMs. Agonist and antagonist assay on receptors were performed using calcium mobilization high-throughput screening (HTS). DH significantly attenuated CH by modulating myocardial contractility, suppressing cell area enlargement and down-regulating ET-1-induced brain natriuretic peptide (BNP), actinin alpha 2 (ACTN2) and cardiac muscle troponin T (TNNT2) protein expression (P < 0.05). Endothelin receptor type B (ETBR) and angiotensin II receptor type 1 (AT1R) were DH direct targets, with IC50 value of 25.67 μL/mL and 1.10 μL/mL, respectively. Proteomics analysis showed that proteins involved in cell cycle inhibition, RNA processing, mitochondrial translation and cytoskeleton are significant regulated by DH treatment. These data revealed that ETBR and AT1R are DH direct targets on protecting against CH, providing a strategy to explore direct targets of CHMPs.
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spelling pubmed-57327362017-12-19 DanHong injection targets endothelin receptor type B and angiotensin II receptor type 1 in protection against cardiac hypertrophy Zhang, Min-Yu Guo, Fei-Fei Wu, Hong-Wei Yu, Yang-Yang Wei, Jun-Ying Wang, Shi-Feng Zhang, Yu-Xin Xian, Ming-Hua Wu, Qing-Hua Zhao, Bu-Chang Li, Shi-You Yang, Hong-Jun Oncotarget Research Paper Cardiac hypertrophy (CH) is an independent risk factor for cardiovascular diseases (CVDs). Mitigating or preventing CH is the most effective strategy for the treatment of CVDs. DanHong injection (DH) is a Chinese herbal medicine preparation (CHMP) widely used in clinical treatment of several CVDs in China. However, the direct targets and cellular mechanisms for these protective effects remain unclear. This study was designed to illustrate the direct targets of DH in protecting against CH and investigate CH molecular pathogenesis. A hypertrophic cell model was induced by endothelin-1 (ET-1) on human induced pluripotent stem cell-derived cardiomyocytes (hiPS-CMs). Real time cellular analysis (RTCA) cardio system and high content analysis (HCA) were used to detect the changes in contractile function, morphology and protein level of hypertrophic hiPS-CMs. Agonist and antagonist assay on receptors were performed using calcium mobilization high-throughput screening (HTS). DH significantly attenuated CH by modulating myocardial contractility, suppressing cell area enlargement and down-regulating ET-1-induced brain natriuretic peptide (BNP), actinin alpha 2 (ACTN2) and cardiac muscle troponin T (TNNT2) protein expression (P < 0.05). Endothelin receptor type B (ETBR) and angiotensin II receptor type 1 (AT1R) were DH direct targets, with IC50 value of 25.67 μL/mL and 1.10 μL/mL, respectively. Proteomics analysis showed that proteins involved in cell cycle inhibition, RNA processing, mitochondrial translation and cytoskeleton are significant regulated by DH treatment. These data revealed that ETBR and AT1R are DH direct targets on protecting against CH, providing a strategy to explore direct targets of CHMPs. Impact Journals LLC 2017-10-13 /pmc/articles/PMC5732736/ /pubmed/29262570 http://dx.doi.org/10.18632/oncotarget.21900 Text en Copyright: © 2017 Zhang et al. http://creativecommons.org/licenses/by/3.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0/) 3.0 (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
spellingShingle Research Paper
Zhang, Min-Yu
Guo, Fei-Fei
Wu, Hong-Wei
Yu, Yang-Yang
Wei, Jun-Ying
Wang, Shi-Feng
Zhang, Yu-Xin
Xian, Ming-Hua
Wu, Qing-Hua
Zhao, Bu-Chang
Li, Shi-You
Yang, Hong-Jun
DanHong injection targets endothelin receptor type B and angiotensin II receptor type 1 in protection against cardiac hypertrophy
title DanHong injection targets endothelin receptor type B and angiotensin II receptor type 1 in protection against cardiac hypertrophy
title_full DanHong injection targets endothelin receptor type B and angiotensin II receptor type 1 in protection against cardiac hypertrophy
title_fullStr DanHong injection targets endothelin receptor type B and angiotensin II receptor type 1 in protection against cardiac hypertrophy
title_full_unstemmed DanHong injection targets endothelin receptor type B and angiotensin II receptor type 1 in protection against cardiac hypertrophy
title_short DanHong injection targets endothelin receptor type B and angiotensin II receptor type 1 in protection against cardiac hypertrophy
title_sort danhong injection targets endothelin receptor type b and angiotensin ii receptor type 1 in protection against cardiac hypertrophy
topic Research Paper
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5732736/
https://www.ncbi.nlm.nih.gov/pubmed/29262570
http://dx.doi.org/10.18632/oncotarget.21900
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