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《Cell，3月16日，BET Inhibition Blocks Inflammation-Induced Cardiac Dysfunction and SARS-CoV-2 Infection》

  • 来源专题：COVID-19科研动态监测
  • 编译者： zhangmin
  • 发布时间：2021-03-23

  • BET Inhibition Blocks Inflammation-Induced Cardiac Dysfunction and SARS-CoV-2 Infection
    Richard J. Mills
    Sean J. Humphrey
    Patrick RJ. Fortuna
    Tobias Bald
    David E. James
    James E. Hudson
    Show all authors
    Published:March 16, 2021DOI:https://doi.org/10.1016/j.cell.2021.03.026

    Summary
    Cardiac injury and dysfunction occur in COVID-19 patients and increase the risk of mortality. Causes are ill defined, but could be direct cardiac infection and/or inflammation-induced dysfunction. To identify mechanisms and cardio-protective drugs, we use a state-of-the-art pipeline combining human cardiac organoids with phosphoproteomics and single nuclei RNA sequencing. We identify an inflammatory ‘cytokine-storm’, a cocktail of interferon gamma, interleukin 1β and poly(I:C), induced diastolic dysfunction. Bromodomain-containing protein 4 is activated along with a viral response that is consistent in both human cardiac organoids and hearts of SARS-CoV-2 infected K18-hACE2 mice. Bromodomain and extraterminal family inhibitors (BETi) recover dysfunction in hCO and completely prevent cardiac dysfunction and death in a mouse cytokine-storm model. Additionally, BETi decreases transcription of genes in the viral response, decreases ACE2 expression and reduces SARS-CoV-2 infection of cardiomyocytes. Together, BETi, including the FDA breakthrough designated drug apabetalone, are promising candidates to prevent COVID-19 mediated cardiac damage.

  • 原文来源：https://www.cell.com/cell/fulltext/S0092-8674(21)00354-8#
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