Phenotypic screening uncovered anti-myocardial fibrosis candidates using a novel 3D myocardial tissue under hypoxia
Myocardial fibrosis (MF) is a common pathological hallmark of cardiovascular diseases, reflecting shared mechanisms in their progression. However, the lack of reliable MF models that accurately mimic its pathogenesis has hindered drug discovery, highlighting the urgent need for more effective therap...
Saved in:
| Main Authors: | , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Elsevier
2025-06-01
|
| Series: | Acta Pharmaceutica Sinica B |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2211383525002874 |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1849433410932572160 |
|---|---|
| author | Jingyu Wang Xiangning Liu Rongxin Zhu Ying Sun Boyang Jiao Keyan Wang Yong Jiang Yong Wang Chun Li Wei Wang |
| author_facet | Jingyu Wang Xiangning Liu Rongxin Zhu Ying Sun Boyang Jiao Keyan Wang Yong Jiang Yong Wang Chun Li Wei Wang |
| author_sort | Jingyu Wang |
| collection | DOAJ |
| description | Myocardial fibrosis (MF) is a common pathological hallmark of cardiovascular diseases, reflecting shared mechanisms in their progression. However, the lack of reliable MF models that accurately mimic its pathogenesis has hindered drug discovery, highlighting the urgent need for more effective therapeutic agents. Herein, a novel contractile three-dimensional (3D) myocardial tissue model integrating cardiomyocytes, cardiac-fibroblasts, and bone marrow-derived macrophages in collagen hydrogel was developed to simulate the fibrotic changes of cardiovascular disease, and facilitate the screening of anti-MF compounds. The 3D myocardial tissue model exhibited precise, visualizable, and quantifiable contractile characteristics under hypoxia and drug interventions. 76 compounds extracted from the resins of Toxicodendron vernicifluum, a traditional Chinese medicine with clear clinical benefits for fibrotic diseases, were screened for anti-fibrotic activity. Using an in vitro 3D oxygen–glucose deprivation (OGD)-treated myocardial tissue model instead of a two-dimensional transforming growth factor-β treated cardiac-fibroblasts model, two candidates including LQ-40 and SQ-3 exert impressive anti-MF activity, which was further validated in left anterior descending coronary artery ligation-induced MF mouse model. The current results demonstrate the feasibility and advantage of the novel contractile 3D tissue model with multi-cell types in discovering candidates for MF, further stressing the great potential of regulating macrophages in the treatment of MF. |
| format | Article |
| id | doaj-art-ecb6e02447d143a39286ce7129abf560 |
| institution | Kabale University |
| issn | 2211-3835 |
| language | English |
| publishDate | 2025-06-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Acta Pharmaceutica Sinica B |
| spelling | doaj-art-ecb6e02447d143a39286ce7129abf5602025-08-20T03:27:02ZengElsevierActa Pharmaceutica Sinica B2211-38352025-06-011563008302410.1016/j.apsb.2025.04.025Phenotypic screening uncovered anti-myocardial fibrosis candidates using a novel 3D myocardial tissue under hypoxiaJingyu Wang0Xiangning Liu1Rongxin Zhu2Ying Sun3Boyang Jiao4Keyan Wang5Yong Jiang6Yong Wang7Chun Li8Wei Wang9School of Traditional Chinese Medicine, Beijing University of Chinese Medicine, Beijing 100029, ChinaSchool of Traditional Chinese Medicine, Beijing University of Chinese Medicine, Beijing 100029, ChinaSchool of Traditional Chinese Medicine, Beijing University of Chinese Medicine, Beijing 100029, ChinaSchool of Traditional Chinese Medicine, Beijing University of Chinese Medicine, Beijing 100029, ChinaSchool of Traditional Chinese Medicine, Beijing University of Chinese Medicine, Beijing 100029, ChinaSchool of Traditional Chinese Medicine, Beijing University of Chinese Medicine, Beijing 100029, ChinaState Key Laboratory of Natural and Biomimetic Drugs, School of Pharmaceutical Sciences, Peking University, Beijing 100191, ChinaDongzhimen Hospital, Beijing University of Chinese Medicine, Beijing 100029, China; Key Laboratory of Traditional Chinese Medicine Syndrome and Formula, Ministry of Education, Beijing 100029, China; Yunnan University of Chinese Medicine, Kunming 650500, China; Corresponding authors.Key Laboratory of Traditional Chinese Medicine Syndrome and Formula, Ministry of Education, Beijing 100029, China; Modern Research Center for Traditional Chinese Medicine, Beijing University of Chinese Medicine, Beijing 100029, China; State Key Laboratory of Traditional Chinese Medicine Syndrome, Guangzhou University of Chinese Medicine, Guangzhou 510006, China; Corresponding authors.Key Laboratory of Traditional Chinese Medicine Syndrome and Formula, Ministry of Education, Beijing 100029, China; State Key Laboratory of Traditional Chinese Medicine Syndrome, Guangzhou University of Chinese Medicine, Guangzhou 510006, China; Corresponding authors.Myocardial fibrosis (MF) is a common pathological hallmark of cardiovascular diseases, reflecting shared mechanisms in their progression. However, the lack of reliable MF models that accurately mimic its pathogenesis has hindered drug discovery, highlighting the urgent need for more effective therapeutic agents. Herein, a novel contractile three-dimensional (3D) myocardial tissue model integrating cardiomyocytes, cardiac-fibroblasts, and bone marrow-derived macrophages in collagen hydrogel was developed to simulate the fibrotic changes of cardiovascular disease, and facilitate the screening of anti-MF compounds. The 3D myocardial tissue model exhibited precise, visualizable, and quantifiable contractile characteristics under hypoxia and drug interventions. 76 compounds extracted from the resins of Toxicodendron vernicifluum, a traditional Chinese medicine with clear clinical benefits for fibrotic diseases, were screened for anti-fibrotic activity. Using an in vitro 3D oxygen–glucose deprivation (OGD)-treated myocardial tissue model instead of a two-dimensional transforming growth factor-β treated cardiac-fibroblasts model, two candidates including LQ-40 and SQ-3 exert impressive anti-MF activity, which was further validated in left anterior descending coronary artery ligation-induced MF mouse model. The current results demonstrate the feasibility and advantage of the novel contractile 3D tissue model with multi-cell types in discovering candidates for MF, further stressing the great potential of regulating macrophages in the treatment of MF.http://www.sciencedirect.com/science/article/pii/S2211383525002874Myocardial fibrosis3D myocardial tissueToxicodendron vernicifluumHypoxiaDrug screeningPrimary cell |
| spellingShingle | Jingyu Wang Xiangning Liu Rongxin Zhu Ying Sun Boyang Jiao Keyan Wang Yong Jiang Yong Wang Chun Li Wei Wang Phenotypic screening uncovered anti-myocardial fibrosis candidates using a novel 3D myocardial tissue under hypoxia Acta Pharmaceutica Sinica B Myocardial fibrosis 3D myocardial tissue Toxicodendron vernicifluum Hypoxia Drug screening Primary cell |
| title | Phenotypic screening uncovered anti-myocardial fibrosis candidates using a novel 3D myocardial tissue under hypoxia |
| title_full | Phenotypic screening uncovered anti-myocardial fibrosis candidates using a novel 3D myocardial tissue under hypoxia |
| title_fullStr | Phenotypic screening uncovered anti-myocardial fibrosis candidates using a novel 3D myocardial tissue under hypoxia |
| title_full_unstemmed | Phenotypic screening uncovered anti-myocardial fibrosis candidates using a novel 3D myocardial tissue under hypoxia |
| title_short | Phenotypic screening uncovered anti-myocardial fibrosis candidates using a novel 3D myocardial tissue under hypoxia |
| title_sort | phenotypic screening uncovered anti myocardial fibrosis candidates using a novel 3d myocardial tissue under hypoxia |
| topic | Myocardial fibrosis 3D myocardial tissue Toxicodendron vernicifluum Hypoxia Drug screening Primary cell |
| url | http://www.sciencedirect.com/science/article/pii/S2211383525002874 |
| work_keys_str_mv | AT jingyuwang phenotypicscreeninguncoveredantimyocardialfibrosiscandidatesusinganovel3dmyocardialtissueunderhypoxia AT xiangningliu phenotypicscreeninguncoveredantimyocardialfibrosiscandidatesusinganovel3dmyocardialtissueunderhypoxia AT rongxinzhu phenotypicscreeninguncoveredantimyocardialfibrosiscandidatesusinganovel3dmyocardialtissueunderhypoxia AT yingsun phenotypicscreeninguncoveredantimyocardialfibrosiscandidatesusinganovel3dmyocardialtissueunderhypoxia AT boyangjiao phenotypicscreeninguncoveredantimyocardialfibrosiscandidatesusinganovel3dmyocardialtissueunderhypoxia AT keyanwang phenotypicscreeninguncoveredantimyocardialfibrosiscandidatesusinganovel3dmyocardialtissueunderhypoxia AT yongjiang phenotypicscreeninguncoveredantimyocardialfibrosiscandidatesusinganovel3dmyocardialtissueunderhypoxia AT yongwang phenotypicscreeninguncoveredantimyocardialfibrosiscandidatesusinganovel3dmyocardialtissueunderhypoxia AT chunli phenotypicscreeninguncoveredantimyocardialfibrosiscandidatesusinganovel3dmyocardialtissueunderhypoxia AT weiwang phenotypicscreeninguncoveredantimyocardialfibrosiscandidatesusinganovel3dmyocardialtissueunderhypoxia |