Andrographolide Promotes Interaction Between Endothelin-Dependent EDNRA/EDNRB and Myocardin-SRF to Regulate Pathological Vascular Remodeling
IntroductionPathological vascular remodeling is a hallmark of various vascular diseases. Smooth muscle cell (SMC) phenotypic switching plays a pivotal role during pathological vascular remodeling. The mechanism of how to regulate SMC phenotypic switching still needs to be defined. This study aims to...
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Frontiers Media S.A.
2022-01-01
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| Series: | Frontiers in Cardiovascular Medicine |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fcvm.2021.783872/full |
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| author | Wangming Hu Xiao Wu Zhong Jin Zheng Wang Qiru Guo Zixian Chen Song Zhu Haidi Zhang Jian Huo Lingling Zhang Xin Zhou Lan Yang Huan Xu Liangqing Shi Yong Wang |
| author_facet | Wangming Hu Xiao Wu Zhong Jin Zheng Wang Qiru Guo Zixian Chen Song Zhu Haidi Zhang Jian Huo Lingling Zhang Xin Zhou Lan Yang Huan Xu Liangqing Shi Yong Wang |
| author_sort | Wangming Hu |
| collection | DOAJ |
| description | IntroductionPathological vascular remodeling is a hallmark of various vascular diseases. Smooth muscle cell (SMC) phenotypic switching plays a pivotal role during pathological vascular remodeling. The mechanism of how to regulate SMC phenotypic switching still needs to be defined. This study aims to investigate the effect of Andrographolide, a key principle isolated from Andrographis paniculate, on pathological vascular remodeling and its underlying mechanism.MethodsA C57/BL6 mouse left carotid artery complete ligation model and rat SMCs were used to determine whether Andrographolide is critical in regulating SMC phenotypic switching. Quantitative real-time PCR, a CCK8 cell proliferation assay, BRDU incorporation assay, Boyden chamber migration assay, and spheroid sprouting assay were performed to evaluate whether Andrographolide suppresses SMC proliferation and migration. Immunohistochemistry staining, immunofluorescence staining, and protein co-immunoprecipitation were used to observe the interaction between EDNRA, EDNRB, and Myocardin-SRF.ResultsAndrographolide inhibits neointimal hyperplasia in the left carotid artery complete ligation model. Andrographolide regulates SMC phenotypic switching characterized by suppressing proliferation and migration. Andrographolide activates the endothelin signaling pathway exhibited by dramatically inducing EDNRA and EDNRB expression. The interaction between EDNRA/EDNRB and Myocardin-SRF resulted in promoting SMC differentiation marker gene expression.ConclusionAndrographolide plays a critical role in regulating pathological vascular remodeling. |
| first_indexed | 2024-12-18T04:53:44Z |
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| id | doaj.art-a9ad23315f754c38bc18ebd3b25892f8 |
| institution | Directory Open Access Journal |
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| language | English |
| last_indexed | 2024-12-18T04:53:44Z |
| publishDate | 2022-01-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Cardiovascular Medicine |
| spelling | doaj.art-a9ad23315f754c38bc18ebd3b25892f82022-12-21T21:20:21ZengFrontiers Media S.A.Frontiers in Cardiovascular Medicine2297-055X2022-01-01810.3389/fcvm.2021.783872783872Andrographolide Promotes Interaction Between Endothelin-Dependent EDNRA/EDNRB and Myocardin-SRF to Regulate Pathological Vascular RemodelingWangming Hu0Xiao Wu1Zhong Jin2Zheng Wang3Qiru Guo4Zixian Chen5Song Zhu6Haidi Zhang7Jian Huo8Lingling Zhang9Xin Zhou10Lan Yang11Huan Xu12Liangqing Shi13Yong Wang14College of Basic Medicine, Chengdu University of Traditional Chinese Medicine, Chengdu, ChinaCollege of Basic Medicine, Chengdu University of Traditional Chinese Medicine, Chengdu, ChinaCollege of Basic Medicine, Chengdu University of Traditional Chinese Medicine, Chengdu, ChinaCollege of Basic Medicine, Chengdu University of Traditional Chinese Medicine, Chengdu, ChinaCollege of Basic Medicine, Chengdu University of Traditional Chinese Medicine, Chengdu, ChinaSchool of Ethnic Medicine, Chengdu University of Traditional Chinese Medicine, Chengdu, ChinaHospital of Chengdu University of Traditional Chinese Medicine, Chengdu University of Traditional Chinese Medicine, Chengdu, ChinaHospital of Chengdu University of Traditional Chinese Medicine, Chengdu University of Traditional Chinese Medicine, Chengdu, ChinaChengdu Women's and Children's Central Hospital, School of Medicine, University of Electronic Science and Technology of China, Chengdu, ChinaCollege of Basic Medicine, Chengdu University of Traditional Chinese Medicine, Chengdu, ChinaCollege of Basic Medicine, Chengdu University of Traditional Chinese Medicine, Chengdu, ChinaCollege of Basic Medicine, Chengdu University of Traditional Chinese Medicine, Chengdu, ChinaCollege of Basic Medicine, Chengdu University of Traditional Chinese Medicine, Chengdu, ChinaCollege of Basic Medicine, Chengdu University of Traditional Chinese Medicine, Chengdu, ChinaCollege of Basic Medicine, Chengdu University of Traditional Chinese Medicine, Chengdu, ChinaIntroductionPathological vascular remodeling is a hallmark of various vascular diseases. Smooth muscle cell (SMC) phenotypic switching plays a pivotal role during pathological vascular remodeling. The mechanism of how to regulate SMC phenotypic switching still needs to be defined. This study aims to investigate the effect of Andrographolide, a key principle isolated from Andrographis paniculate, on pathological vascular remodeling and its underlying mechanism.MethodsA C57/BL6 mouse left carotid artery complete ligation model and rat SMCs were used to determine whether Andrographolide is critical in regulating SMC phenotypic switching. Quantitative real-time PCR, a CCK8 cell proliferation assay, BRDU incorporation assay, Boyden chamber migration assay, and spheroid sprouting assay were performed to evaluate whether Andrographolide suppresses SMC proliferation and migration. Immunohistochemistry staining, immunofluorescence staining, and protein co-immunoprecipitation were used to observe the interaction between EDNRA, EDNRB, and Myocardin-SRF.ResultsAndrographolide inhibits neointimal hyperplasia in the left carotid artery complete ligation model. Andrographolide regulates SMC phenotypic switching characterized by suppressing proliferation and migration. Andrographolide activates the endothelin signaling pathway exhibited by dramatically inducing EDNRA and EDNRB expression. The interaction between EDNRA/EDNRB and Myocardin-SRF resulted in promoting SMC differentiation marker gene expression.ConclusionAndrographolide plays a critical role in regulating pathological vascular remodeling.https://www.frontiersin.org/articles/10.3389/fcvm.2021.783872/fullAndrographolideEDNRAEDNRBMyocardin-SRFCArG boxpathological vascular remodeling |
| spellingShingle | Wangming Hu Xiao Wu Zhong Jin Zheng Wang Qiru Guo Zixian Chen Song Zhu Haidi Zhang Jian Huo Lingling Zhang Xin Zhou Lan Yang Huan Xu Liangqing Shi Yong Wang Andrographolide Promotes Interaction Between Endothelin-Dependent EDNRA/EDNRB and Myocardin-SRF to Regulate Pathological Vascular Remodeling Frontiers in Cardiovascular Medicine Andrographolide EDNRA EDNRB Myocardin-SRF CArG box pathological vascular remodeling |
| title | Andrographolide Promotes Interaction Between Endothelin-Dependent EDNRA/EDNRB and Myocardin-SRF to Regulate Pathological Vascular Remodeling |
| title_full | Andrographolide Promotes Interaction Between Endothelin-Dependent EDNRA/EDNRB and Myocardin-SRF to Regulate Pathological Vascular Remodeling |
| title_fullStr | Andrographolide Promotes Interaction Between Endothelin-Dependent EDNRA/EDNRB and Myocardin-SRF to Regulate Pathological Vascular Remodeling |
| title_full_unstemmed | Andrographolide Promotes Interaction Between Endothelin-Dependent EDNRA/EDNRB and Myocardin-SRF to Regulate Pathological Vascular Remodeling |
| title_short | Andrographolide Promotes Interaction Between Endothelin-Dependent EDNRA/EDNRB and Myocardin-SRF to Regulate Pathological Vascular Remodeling |
| title_sort | andrographolide promotes interaction between endothelin dependent ednra ednrb and myocardin srf to regulate pathological vascular remodeling |
| topic | Andrographolide EDNRA EDNRB Myocardin-SRF CArG box pathological vascular remodeling |
| url | https://www.frontiersin.org/articles/10.3389/fcvm.2021.783872/full |
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