ArticleCell2024
Multiscale drug screening for cardiac fibrosis identifies MD2 as a therapeutic target.
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Article in Cell, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 53 papers.
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53citing papers in PubMed
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Who cites it
53 citing papers in PubMed.
- MMP12 induces fibrogenic macrophage differentiation to drive granuloma-associated cardiac fibrosis.American journal of respiratory and critical care medicine · 2026Article
- Reconstructing AF-associated atrial fibrosis: Patient-specific iPSC models, fit-for-purpose atrial microphysiological systems, and nanomedicine.Materials today. Bio · 2026Review
- New approach methodologies: drug screening platform to identify antifibrotic compounds.Nature protocols · 2026Review
- Integrated Scaffold Redesign and iPSC-Based Screening Reveal Potent Antifibrotic Artemisinin Analogs in Systemic Sclerosis Models.ACS central science · 2026Article
- Ellagic acid attenuates myocardial fibrosis by suppressing Bmi1-mediated inhibition of the p53/p21 pathway in cardiac fibroblasts.Molecular and cellular biochemistry · 2026Article
- AI-Powered Detection of Left Ventricular Myocardial Scar from Dual-Sequence CT: Global and Segmental Prediction Validated by CMR.Journal of imaging informatics in medicine · 2026Article
- Screening of anti-metastasis drugs by targeting angiopellosis and cancer cluster extravasation.Science advances · 2026Article
- A practical toolbox for modelling fibrosis in vitro.Nature biomedical engineering · 2026Review
- Article
- FAP-targeted gastrodin nanoparticles in responsive hydrogel alleviate cardiac fibrosis via fibroblast metabolic reprogramming.Bioactive materials · 2026Article
- Artesunate-based macromolecular therapy attenuates neutrophilic asthma by targeting the BCAT1/Succinate/NLRP3 metabolite-immunity cascade.Journal of nanobiotechnology · 2026Article
- S100A4 Orchestrates Fibroblast Fate to Drive Fibrotic Remodeling.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2026Article
- Efficient multi-lineage cardiovascular differentiation of human pluripotent stem cells in animal serum-free conditions.Scientific reports · 2026Article
- The Role of High-Mobility Group Box 1/Toll-Like Receptor 4 in Pericardial Fibrosis and Postoperative Low Cardiac Output Syndrome in Constrictive Pericarditis.Cardiology research · 2026Article
- Artesunate Ameliorates APAP-induced Liver Injury by Promoting NEDD4L-Mediated Ubiquitination and Degradation of TXNIP.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Artesunate directly targeting MMP9 to reduce angiogenesis and increase CD8 + T cell infiltration inhibits hepatocellular carcinoma.Cancer cell international · 2026Article
- The impact of inflammation, neuromodulation, and gut microbiota on developing cardiac fibrosis and hypertension.Cardiovascular research · 2026Review
- Reimagining human-centric drug development with new approach methodologies.Science (New York, N.Y.) · 2026Review
- Review
- Versatile hiPSC Models and Bioengineering Platforms for Investigation of Atrial Fibrosis and Fibrillation.Cells · 2026Review
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Authors and funding
17 authors.
Hao ZhangStanford Cardiovascular Institute, Stanford University School of Medicine, Stanford, CA 94305, USA; Institute for Stem Cell Biology and Regenerative Medicine, Stanford University School of Medicine, Stanford, CA 94305, USA; Department of Medicine, Division of Cardiovascular Medicine, Stanford University School of Medicine, Stanford, CA 94305, USA. Electronic address: zhanghao@stanford.edu.
Phung N ThaiDepartment of Internal Medicine, Division of Cardiovascular Medicine, University of California, Davis, Davis, CA 95616, USA; David Geffen School of Medicine at University of California, Los Angeles, CA 90095, USA.
Rabindra V ShivnaraineGreenstone Biosciences, Palo Alto, CA 94305, USA.
Lu RenStanford Cardiovascular Institute, Stanford University School of Medicine, Stanford, CA 94305, USA; Institute for Stem Cell Biology and Regenerative Medicine, Stanford University School of Medicine, Stanford, CA 94305, USA; Department of Medicine, Division of Cardiovascular Medicine, Stanford University School of Medicine, Stanford, CA 94305, USA.
Xuekun WuStanford Cardiovascular Institute, Stanford University School of Medicine, Stanford, CA 94305, USA; Institute for Stem Cell Biology and Regenerative Medicine, Stanford University School of Medicine, Stanford, CA 94305, USA; Department of Medicine, Division of Cardiovascular Medicine, Stanford University School of Medicine, Stanford, CA 94305, USA.
Dirk H SiepeDepartment of Experimental Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
Yu LiuStanford Cardiovascular Institute, Stanford University School of Medicine, Stanford, CA 94305, USA; Institute for Stem Cell Biology and Regenerative Medicine, Stanford University School of Medicine, Stanford, CA 94305, USA; Department of Medicine, Division of Cardiovascular Medicine, Stanford University School of Medicine, Stanford, CA 94305, USA.
Chengyi TuStanford Cardiovascular Institute, Stanford University School of Medicine, Stanford, CA 94305, USA; Institute for Stem Cell Biology and Regenerative Medicine, Stanford University School of Medicine, Stanford, CA 94305, USA; Department of Medicine, Division of Cardiovascular Medicine, Stanford University School of Medicine, Stanford, CA 94305, USA.
Hye Sook ShinStanford Cardiovascular Institute, Stanford University School of Medicine, Stanford, CA 94305, USA; Institute for Stem Cell Biology and Regenerative Medicine, Stanford University School of Medicine, Stanford, CA 94305, USA; Department of Medicine, Division of Cardiovascular Medicine, Stanford University School of Medicine, Stanford, CA 94305, USA.
Arianne CaudalStanford Cardiovascular Institute, Stanford University School of Medicine, Stanford, CA 94305, USA; Institute for Stem Cell Biology and Regenerative Medicine, Stanford University School of Medicine, Stanford, CA 94305, USA; Department of Medicine, Division of Cardiovascular Medicine, Stanford University School of Medicine, Stanford, CA 94305, USA.
Souhrid MukherjeeGreenstone Biosciences, Palo Alto, CA 94305, USA.
Jeremy LeitzGreenstone Biosciences, Palo Alto, CA 94305, USA.
Wilson Tan Lek WenStanford Cardiovascular Institute, Stanford University School of Medicine, Stanford, CA 94305, USA; Institute for Stem Cell Biology and Regenerative Medicine, Stanford University School of Medicine, Stanford, CA 94305, USA; Department of Medicine, Division of Cardiovascular Medicine, Stanford University School of Medicine, Stanford, CA 94305, USA.
Wenqiang LiuStanford Cardiovascular Institute, Stanford University School of Medicine, Stanford, CA 94305, USA; Institute for Stem Cell Biology and Regenerative Medicine, Stanford University School of Medicine, Stanford, CA 94305, USA; Department of Medicine, Division of Cardiovascular Medicine, Stanford University School of Medicine, Stanford, CA 94305, USA.
Wenjuan ZhuStanford Cardiovascular Institute, Stanford University School of Medicine, Stanford, CA 94305, USA; Institute for Stem Cell Biology and Regenerative Medicine, Stanford University School of Medicine, Stanford, CA 94305, USA; Department of Medicine, Division of Cardiovascular Medicine, Stanford University School of Medicine, Stanford, CA 94305, USA.
Nipavan ChiamvimonvatDepartment of Internal Medicine, Division of Cardiovascular Medicine, University of California, Davis, Davis, CA 95616, USA; Department of Basic Medical Sciences and Translational Cardiovascular Research Center, University of Arizona College of Medicine, Phoenix, AZ 85004, USA.
Joseph C WuStanford Cardiovascular Institute, Stanford University School of Medicine, Stanford, CA 94305, USA; Institute for Stem Cell Biology and Regenerative Medicine, Stanford University School of Medicine, Stanford, CA 94305, USA; Department of Medicine, Division of Cardiovascular Medicine, Stanford University School of Medicine, Stanford, CA 94305, USA. Electronic address: joewu@stanford.edu.
Funding
Project 3 (Mercola)P01HL141084 · NHLBI · STANFORD UNIVERSITY · PI Joseph C. Wu · 2019 to 2026
$21.1MElucidating Mechanism of Cardiac Fibrosis with Cell Village of Pooled Human iPSCsR01HL130020 · NHLBI · STANFORD UNIVERSITY · PI Ronglih Liao, MARK MERCOLA · 2016 to 2026
$7.3MFunctional Interactions of Cardiac Ion ChannelsR01HL085844 · NHLBI · UNIVERSITY OF CALIFORNIA AT DAVIS · PI CHIAMVIMONVAT, NIPAVAN · 2007 to 2025
$7.3MTraining Program In Basic & Translational Cardiovascular ScienceT32HL086350 · NHLBI · UNIVERSITY OF CALIFORNIA AT DAVIS · PI Martin Cadeiras, David A. Liem · 2008 to 2026
$7.1MHuman Induced Pluripotent Stem Cells for Cardiovascular Disease ModelingR01HL113006 · NHLBI · STANFORD UNIVERSITY · PI WU, JOSEPH C. · 2012 to 2025
$6.8MHuman iPSCs for Elucidating Intercellular Crosstalk Signaling in Dilated CardiomyopathyR01HL141371 · NHLBI · STANFORD UNIVERSITY · PI WONG, WING H., WU, JOSEPH C. · 2018 to 2025
$6.2MTranslational Study of Cardiac DysfunctionR01HL085727 · NHLBI · UNIVERSITY OF CALIFORNIA AT DAVIS · PI CHIAMVIMONVAT, NIPAVAN, SIRISH, PADMINI · 2008 to 2022
$5.7MHuman iPSC Model to Elucidate Metabolic Interplay in Diabetic CardimyopathyR01HL146690 · NHLBI · STANFORD UNIVERSITY · PI LIAO, RONGLIH, MERCOLA, MARK · 2019 to 2025
$5.1MElucidating Anthracycline-Induced Cell Type-Specific Cardiovascular Toxicity with CRISPRi/a ScreensR01HL150693 · NHLBI · STANFORD UNIVERSITY · PI Ronglih Liao, Joseph C. Wu · 2021 to 2026
$4.1MElucidating ECM Signaling in Cardiac Organoids with Machine Learning and Single-cell MultiomicsR01HL163680 · NHLBI · STANFORD UNIVERSITY · PI RAJADAS, JAYAKUMAR, WONG, WING H. · 2022 to 2025
$2.5MA prospective multiethnic HFpEF cohort from Californias Central ValleyU01HL160274 · NHLBI · UNIVERSITY OF CALIFORNIA AT DAVIS · PI Martin Cadeiras, Nipavan Chiamvimonvat · 2021 to 2026
$2.3MMolecular Mechanisms of Atrial Fibrillation: A Multimodal AnalysisR01HL170520 · NHLBI · UNIVERSITY OF CALIFORNIA AT DAVIS · PI Nipavan Chiamvimonvat, Vladimir Filkov · 2024 to 2026
$1.8MAmerican Heart Association-American Stroke Association 24POST1198753American Heart Association-American Stroke Association 908936NHLBI NIH HHS F32 HL173968NHLBI NIH HHS K99 HL164962NHLBI NIH HHS P01 HL141084NHLBI NIH HHS R01 HL085727NHLBI NIH HHS R01 HL085844NHLBI NIH HHS R01 HL113006NHLBI NIH HHS R01 HL130020NHLBI NIH HHS R01 HL141371NHLBI NIH HHS R01 HL146690NHLBI NIH HHS R01 HL150693NHLBI NIH HHS R01 HL163680NHLBI NIH HHS R01 HL170520NHLBI NIH HHS R56 HL167932NHLBI NIH HHS T32 HL086350NHLBI NIH HHS U01 HL160274NIH HHS S10 OD010389NIH HHS S10 OD026899
Abstract
Cardiac fibrosis impairs cardiac function, but no effective clinical therapies exist. To address this unmet need, we employed a high-throughput screening for antifibrotic compounds using human induced pluripotent stem cell (iPSC)-derived cardiac fibroblasts (CFs). Counter-screening of the initial candidates using iPSC-derived cardiomyocytes and iPSC-derived endothelial cells excluded hits with cardiotoxicity. This screening process identified artesunate as the lead compound. Following profibrotic stimuli, artesunate inhibited proliferation, migration, and contraction in human primary CFs, reduced collagen deposition, and improved contractile function in 3D-engineered heart tissues. Artesunate also attenuated cardiac fibrosis and improved cardiac function in heart failure mouse models. Mechanistically, artesunate targeted myeloid differentiation factor 2 (MD2) and inhibited MD2/Toll-like receptor 4 (TLR4) signaling pathway, alleviating fibrotic gene expression in CFs. Our study leverages multiscale drug screening that integrates a human iPSC platform, tissue engineering, animal models, in silico simulations, and multiomics to identify MD2 as a therapeutic target for cardiac fibrosis.
Indexed as
Drug Evaluation, PreclinicalFibrosisInduced Pluripotent Stem CellsLymphocyte Antigen 96Myocytes, CardiacAnimalsCell ProliferationDisease Models, AnimalFibroblastsHeart FailureHigh-Throughput Screening AssaysHumansMaleMiceMice, Inbred C57BLMyocardiumLymphocyte Antigen 96Toll-Like Receptor 4artesunatecardiac fibrosiscardiovasculardrug screeninginduced pluripotent stem cells
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