Guanxinning injection ameliorates cardiac remodeling in HF mouse and 3D heart spheroid models via p38/FOS/MMP1-mediated inhibition of myocardial hypertrophy and fibrosis
Background: Heart failure (HF) is a cardiovascular disease with high morbidity and mortality. Guanxinning injection (GXNI) is clinically used for the treatment of coronary heart disease, but its therapeutic efficacy and potential mechanism for HF are poorly understood. This study aimed to evaluate t...
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| Format: | Article |
| Language: | English |
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Elsevier
2023-06-01
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| Series: | Biomedicine & Pharmacotherapy |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S0753332223004304 |
| _version_ | 1797837180325855232 |
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| author | Siwen Fan Guangxu Xiao Jingyu Ni Yuhan Zhao Hongying Du Yingran Liang Ming Lv Shuang He Guanwei Fan Yan Zhu |
| author_facet | Siwen Fan Guangxu Xiao Jingyu Ni Yuhan Zhao Hongying Du Yingran Liang Ming Lv Shuang He Guanwei Fan Yan Zhu |
| author_sort | Siwen Fan |
| collection | DOAJ |
| description | Background: Heart failure (HF) is a cardiovascular disease with high morbidity and mortality. Guanxinning injection (GXNI) is clinically used for the treatment of coronary heart disease, but its therapeutic efficacy and potential mechanism for HF are poorly understood. This study aimed to evaluate the therapeutic potential of GXNI on HF, with a special focus on its role in myocardial remodeling. Methods: 3D cardiac organoids and transverse aortic constriction (TAC) mouse models were established and utilized. Heart function and pathology were evaluated by echocardiography, hemodynamic examination, tail-cuff blood pressure and histopathology. Key targets and pathways regulated by GXNI in HF mouse heart were revealed via RNA-seq and network pharmacology analysis, and were verified by RT-PCR, Western blot, immunohistochemistry and immunofluorescence. Results: GXNI significantly inhibited cardiac hypertrophy and cells death. It protected mitochondrial function in cardiac hypertrophic organoids and markedly improved cardiac function in HF mice. Analysis of GXNI-regulated genes in HF mouse hearts revealed that IL-17A signaling in fibroblasts and the corresponding p38/c-Fos/Mmp1 pathway prominently mediated cardiac. Altered expressions of c-Fos, p38 and Mmp1 by GXNI in heart tissues and in cardiac organoids were validated by RT-PCR, WB, IHC, and IF. H&E and Masson staining confirmed that GXNI substantially ameliorated myocardial hypertrophy and fibrosis in HF mice and in 3D organoids. Conclusion: GXNI inhibited cardiac fibrosis and hypertrophy mainly via down-regulating p38/c-Fos/Mmp1 pathway, thereby ameliorating cardiac remodeling in HF mice. Findings in this study provide a new strategy for the clinical application of GXNI in the treatment of heart failure. |
| first_indexed | 2024-04-09T15:20:41Z |
| format | Article |
| id | doaj.art-9a675dfd617f4cf3a95507108468d90a |
| institution | Directory Open Access Journal |
| issn | 0753-3322 |
| language | English |
| last_indexed | 2024-04-09T15:20:41Z |
| publishDate | 2023-06-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Biomedicine & Pharmacotherapy |
| spelling | doaj.art-9a675dfd617f4cf3a95507108468d90a2023-04-29T14:46:09ZengElsevierBiomedicine & Pharmacotherapy0753-33222023-06-01162114642Guanxinning injection ameliorates cardiac remodeling in HF mouse and 3D heart spheroid models via p38/FOS/MMP1-mediated inhibition of myocardial hypertrophy and fibrosisSiwen Fan0Guangxu Xiao1Jingyu Ni2Yuhan Zhao3Hongying Du4Yingran Liang5Ming Lv6Shuang He7Guanwei Fan8Yan Zhu9State Key Laboratory of Component-based Chinese Medicine and Tianjin Haihe Laboratory of Modern Chinese Medicine, Tianjin University of Traditional Chinese Medicine, Beihua South Road, JingHai District, Tianjin 301617, ChinaState Key Laboratory of Component-based Chinese Medicine and Tianjin Haihe Laboratory of Modern Chinese Medicine, Tianjin University of Traditional Chinese Medicine, Beihua South Road, JingHai District, Tianjin 301617, ChinaState Key Laboratory of Component-based Chinese Medicine and Tianjin Haihe Laboratory of Modern Chinese Medicine, Tianjin University of Traditional Chinese Medicine, Beihua South Road, JingHai District, Tianjin 301617, China; Tianjin Key Laboratory of Translational Research of TCM Prescription and Syndrome, First Teaching Hospital of Tianjin University of Traditional Chinese Medicine, Tianjin 300193, ChinaState Key Laboratory of Component-based Chinese Medicine and Tianjin Haihe Laboratory of Modern Chinese Medicine, Tianjin University of Traditional Chinese Medicine, Beihua South Road, JingHai District, Tianjin 301617, ChinaState Key Laboratory of Component-based Chinese Medicine and Tianjin Haihe Laboratory of Modern Chinese Medicine, Tianjin University of Traditional Chinese Medicine, Beihua South Road, JingHai District, Tianjin 301617, ChinaState Key Laboratory of Component-based Chinese Medicine and Tianjin Haihe Laboratory of Modern Chinese Medicine, Tianjin University of Traditional Chinese Medicine, Beihua South Road, JingHai District, Tianjin 301617, ChinaState Key Laboratory of Component-based Chinese Medicine and Tianjin Haihe Laboratory of Modern Chinese Medicine, Tianjin University of Traditional Chinese Medicine, Beihua South Road, JingHai District, Tianjin 301617, ChinaState Key Laboratory of Component-based Chinese Medicine and Tianjin Haihe Laboratory of Modern Chinese Medicine, Tianjin University of Traditional Chinese Medicine, Beihua South Road, JingHai District, Tianjin 301617, ChinaState Key Laboratory of Component-based Chinese Medicine and Tianjin Haihe Laboratory of Modern Chinese Medicine, Tianjin University of Traditional Chinese Medicine, Beihua South Road, JingHai District, Tianjin 301617, China; Tianjin Key Laboratory of Translational Research of TCM Prescription and Syndrome, First Teaching Hospital of Tianjin University of Traditional Chinese Medicine, Tianjin 300193, ChinaState Key Laboratory of Component-based Chinese Medicine and Tianjin Haihe Laboratory of Modern Chinese Medicine, Tianjin University of Traditional Chinese Medicine, Beihua South Road, JingHai District, Tianjin 301617, China; Corresponding author.Background: Heart failure (HF) is a cardiovascular disease with high morbidity and mortality. Guanxinning injection (GXNI) is clinically used for the treatment of coronary heart disease, but its therapeutic efficacy and potential mechanism for HF are poorly understood. This study aimed to evaluate the therapeutic potential of GXNI on HF, with a special focus on its role in myocardial remodeling. Methods: 3D cardiac organoids and transverse aortic constriction (TAC) mouse models were established and utilized. Heart function and pathology were evaluated by echocardiography, hemodynamic examination, tail-cuff blood pressure and histopathology. Key targets and pathways regulated by GXNI in HF mouse heart were revealed via RNA-seq and network pharmacology analysis, and were verified by RT-PCR, Western blot, immunohistochemistry and immunofluorescence. Results: GXNI significantly inhibited cardiac hypertrophy and cells death. It protected mitochondrial function in cardiac hypertrophic organoids and markedly improved cardiac function in HF mice. Analysis of GXNI-regulated genes in HF mouse hearts revealed that IL-17A signaling in fibroblasts and the corresponding p38/c-Fos/Mmp1 pathway prominently mediated cardiac. Altered expressions of c-Fos, p38 and Mmp1 by GXNI in heart tissues and in cardiac organoids were validated by RT-PCR, WB, IHC, and IF. H&E and Masson staining confirmed that GXNI substantially ameliorated myocardial hypertrophy and fibrosis in HF mice and in 3D organoids. Conclusion: GXNI inhibited cardiac fibrosis and hypertrophy mainly via down-regulating p38/c-Fos/Mmp1 pathway, thereby ameliorating cardiac remodeling in HF mice. Findings in this study provide a new strategy for the clinical application of GXNI in the treatment of heart failure.http://www.sciencedirect.com/science/article/pii/S0753332223004304Guanxinning injectionHeart failureCardiac spheroidsCardiac remodelingFOSIL-17A signaling pathway |
| spellingShingle | Siwen Fan Guangxu Xiao Jingyu Ni Yuhan Zhao Hongying Du Yingran Liang Ming Lv Shuang He Guanwei Fan Yan Zhu Guanxinning injection ameliorates cardiac remodeling in HF mouse and 3D heart spheroid models via p38/FOS/MMP1-mediated inhibition of myocardial hypertrophy and fibrosis Biomedicine & Pharmacotherapy Guanxinning injection Heart failure Cardiac spheroids Cardiac remodeling FOS IL-17A signaling pathway |
| title | Guanxinning injection ameliorates cardiac remodeling in HF mouse and 3D heart spheroid models via p38/FOS/MMP1-mediated inhibition of myocardial hypertrophy and fibrosis |
| title_full | Guanxinning injection ameliorates cardiac remodeling in HF mouse and 3D heart spheroid models via p38/FOS/MMP1-mediated inhibition of myocardial hypertrophy and fibrosis |
| title_fullStr | Guanxinning injection ameliorates cardiac remodeling in HF mouse and 3D heart spheroid models via p38/FOS/MMP1-mediated inhibition of myocardial hypertrophy and fibrosis |
| title_full_unstemmed | Guanxinning injection ameliorates cardiac remodeling in HF mouse and 3D heart spheroid models via p38/FOS/MMP1-mediated inhibition of myocardial hypertrophy and fibrosis |
| title_short | Guanxinning injection ameliorates cardiac remodeling in HF mouse and 3D heart spheroid models via p38/FOS/MMP1-mediated inhibition of myocardial hypertrophy and fibrosis |
| title_sort | guanxinning injection ameliorates cardiac remodeling in hf mouse and 3d heart spheroid models via p38 fos mmp1 mediated inhibition of myocardial hypertrophy and fibrosis |
| topic | Guanxinning injection Heart failure Cardiac spheroids Cardiac remodeling FOS IL-17A signaling pathway |
| url | http://www.sciencedirect.com/science/article/pii/S0753332223004304 |
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