心脏毒性
类有机物
心肌梗塞
药品
医学
缺氧(环境)
心脏病学
梗塞
内科学
药理学
化学
生物
毒性
氧气
神经科学
有机化学
作者
Dylan Richards,Yang Li,Charles M. Kerr,Jenny Yao,Gyda Beeson,Robert C. Coyle,Xun Chen,Jia Jia,Brooke J. Damon,Robert Wilson,E. Starr Hazard,Gary Hardiman,Donald R. Menick,Craig C. Beeson,Hai Yao,Tong Ye,Ying Mei
标识
DOI:10.1038/s41551-020-0539-4
摘要
Environmental factors are the largest contributors to cardiovascular disease. Here we show that cardiac organoids that incorporate an oxygen-diffusion gradient and that are stimulated with the neurotransmitter noradrenaline model the structure of the human heart after myocardial infarction (by mimicking the infarcted, border and remote zones), and recapitulate hallmarks of myocardial infarction (in particular, pathological metabolic shifts, fibrosis and calcium handling) at the transcriptomic, structural and functional levels. We also show that the organoids can model hypoxia-enhanced doxorubicin cardiotoxicity. Human organoids that model diseases with non-genetic pathological factors could help with drug screening and development. Cardiac organoids incorporating an oxygen-diffusion gradient and stimulated with the neurotransmitter noradrenaline can model the structure and function of the human heart after myocardial infarction.
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