Spaceflight- induced contractile and mitochondrial dysfunction in an automated heart- on- a- chip platform

• 成果类型: Article
• 署名作者: Mair, Devin B.; Tsui, Jonathan H.; Higashi, Ty; Koenig, Paul; Dong, Zhipeng; Chen, Jeffrey F.; Meir, Jessica U.; Smith, Alec S. T.; Lee, Peter H. U.; Ahn, Eun Hyun; Countryman, Stefanie; Sniadecki, Nathan J.; Kim, Deok - Ho
• 署名单位: Johns Hopkins University; University of Washington; University of Washington Seattle; University of Colorado System; University of Colorado Boulder; National Aeronautics & Space Administration (NASA); University of Washington; University of Washington Seattle; Brown University; Johns Hopkins University; University of Washington; University of Washington Seattle; University of Washington; University of Washington Seattle; University of Washington; University of Washington Seattle; Johns Hopkins University; Johns Hopkins University; Johns Hopkins University
• 刊物名称: PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
• ISSN/ISSBN: 0027-9062
• DOI: 10.1073/pnas.2404644121
• 发表日期: 2024-10-01
• 关键词: tissue; interleukin-18; activation; expression; stress; muscle; beta

摘要

With current plans for manned missions to Mars and beyond, the need to better understand, prevent, and counteract the harmful effects of long- duration spaceflight on the body is becoming increasingly important. In this study, an automated heart- on- a- chip platform was flown to the International Space Station on a 1-mo mission during which contractile cardiac function was monitored in real- time. Upon return to Earth, engineered human heart tissues (EHTs) were further analyzed with ultrastructural imaging and RNA sequencing to investigate the impact of prolonged microgravity on cardiomyocyte function and health. Spaceflight EHTs exhibited significantly reduced twitch forces, increased incidences of arrhythmias, and increased signs of sarcomere disruption and mitochondrial damage. Transcriptomic analyses showed an up- regulation of genes and pathways associated with metabolic disorders, heart failure, oxidative stress, and inflammation, while genes related to contractility and calcium signaling showed significant down- regulation. Finally, in silico modeling revealed a potential link between oxidative stress and mitochondrial dysfunction that corresponded with RNA sequencing results. This represents an in vitro model to faithfully reproduce the adverse effects of spaceflight on three- dimensional (3D)- engineered heart tissue.