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Engineered model of heart tissue repair for exploring fibrotic processes and therapeutic interventions.
Yang, Pengcheng; Zhu, Lihang; Wang, Shiya; Gong, Jixing; Selvaraj, Jonathan Nimal; Ye, Lincai; Chen, Hanxiao; Zhang, Yaoyao; Wang, Gongxin; Song, Wanjun; Li, Zilong; Cai, Lin; Zhang, Hao; Zhang, Donghui.
Afiliação
  • Yang P; State Key Laboratory of Biocatalysis and Enzyme Engineering, School of Life Sciences, Hubei University, Wuhan, China.
  • Zhu L; Department of Biological Repositories, Frontier Science Center for Immunology and Metabolism, Medical Research Institute, Zhongnan Hospital of Wuhan University, Wuhan University, Wuhan, China.
  • Wang S; State Key Laboratory of Biocatalysis and Enzyme Engineering, School of Life Sciences, Hubei University, Wuhan, China.
  • Gong J; Center of Translational Medicine, The First Affiliated Hospital, Zhongshan School of Medicine, Sun Yat-Sen University, Guangdong, China.
  • Selvaraj JN; State Key Laboratory of Biocatalysis and Enzyme Engineering, School of Life Sciences, Hubei University, Wuhan, China.
  • Ye L; Shanghai Institute for Congenital Heart Diseases, Shanghai Children's Medical Center, National Children's Medical Center, Shanghai, China.
  • Chen H; Key Laboratory of Birth Defects and Related Diseases of Women and Children of MOE, Department of Pediatrics, West China Second University Hospital, Sichuan University, Chengdu, China.
  • Zhang Y; Key Laboratory of Birth Defects and Related Diseases of Women and Children of MOE, Department of Pediatrics, West China Second University Hospital, Sichuan University, Chengdu, China.
  • Wang G; Henan SCOPE Research Institute of Electrophysiology Co. Ltd., Kaifeng, China.
  • Song W; Beijing Geek Gene Technology Co. Ltd., Beijing, China.
  • Li Z; State Key Laboratory of Biocatalysis and Enzyme Engineering, School of Life Sciences, Hubei University, Wuhan, China.
  • Cai L; State Key Laboratory of Biocatalysis and Enzyme Engineering, School of Life Sciences, Hubei University, Wuhan, China. cailin12@hubu.edu.cn.
  • Zhang H; Shanghai Institute for Congenital Heart Diseases, Shanghai Children's Medical Center, National Children's Medical Center, Shanghai, China. Drzhanghao@yahoo.com.
  • Zhang D; State Key Laboratory of Biocatalysis and Enzyme Engineering, School of Life Sciences, Hubei University, Wuhan, China. Dongh.zhang@hubu.edu.cn.
Nat Commun ; 15(1): 7996, 2024 Sep 12.
Article em En | MEDLINE | ID: mdl-39266508
ABSTRACT
Advancements in human-engineered heart tissue have enhanced the understanding of cardiac cellular alteration. Nevertheless, a human model simulating pathological remodeling following myocardial infarction for therapeutic development remains essential. Here we develop an engineered model of myocardial repair that replicates the phased remodeling process, including hypoxic stress, fibrosis, and electrophysiological dysfunction. Transcriptomic analysis identifies nine critical signaling pathways related to cellular fate transitions, leading to the evaluation of seventeen modulators for their therapeutic potential in a mini-repair model. A scoring system quantitatively evaluates the restoration of abnormal electrophysiology, demonstrating that the phased combination of TGFß inhibitor SB431542, Rho kinase inhibitor Y27632, and WNT activator CHIR99021 yields enhanced functional restoration compared to single factor treatments in both engineered and mouse myocardial infarction model. This engineered heart tissue repair model effectively captures the phased remodeling following myocardial infarction, providing a crucial platform for discovering therapeutic targets for ischemic heart disease.
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Piridinas / Fibrose / Engenharia Tecidual / Dioxóis / Infarto do Miocárdio Limite: Animals / Humans / Male Idioma: En Revista: Nat Commun Assunto da revista: BIOLOGIA / CIENCIA Ano de publicação: 2024 Tipo de documento: Article País de afiliação: China
Texto completo
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Piridinas / Fibrose / Engenharia Tecidual / Dioxóis / Infarto do Miocárdio Limite: Animals / Humans / Male Idioma: En Revista: Nat Commun Assunto da revista: BIOLOGIA / CIENCIA Ano de publicação: 2024 Tipo de documento: Article País de afiliação: China