BET Inhibition Blocks Inflammation-Induced Cardiac Dysfunction and SARS-CoV-2 Infection
Field | Value | Language |
dc.contributor.author | Mills, Richard J. | en_AU |
dc.contributor.author | Humphrey, Sean J. | en_AU |
dc.contributor.author | Fortuna, Patrick RJ. | en_AU |
dc.contributor.author | Lor, Mary | en_AU |
dc.contributor.author | Foster, Simon R. | en_AU |
dc.contributor.author | Quaife-Ryan, Gregory A. | en_AU |
dc.contributor.author | Johnston, Rebecca L. | en_AU |
dc.contributor.author | Dumenil, Troy | en_AU |
dc.contributor.author | Bishop, Cameron | en_AU |
dc.contributor.author | Ruraraju, Rajeev | en_AU |
dc.contributor.author | Rawle, Daniel J. | en_AU |
dc.contributor.author | Le, Thuy | en_AU |
dc.contributor.author | Zhao, Wei | en_AU |
dc.contributor.author | Lee, Leo | en_AU |
dc.contributor.author | Mackenzie-Kludas, Charley | en_AU |
dc.contributor.author | Mehdiabadi, Neda R. | en_AU |
dc.contributor.author | Halliday, Christopher | en_AU |
dc.contributor.author | Gilham, Dean | en_AU |
dc.contributor.author | Fu, Li | en_AU |
dc.contributor.author | Nicholls, Stephen J. | en_AU |
dc.contributor.author | Johansson, Jan | en_AU |
dc.contributor.author | Sweeney, Michael | en_AU |
dc.contributor.author | Wong, Norman C.W. | en_AU |
dc.contributor.author | Kulikowski, Ewelina | en_AU |
dc.contributor.author | Sokolowski, Kamil A. | en_AU |
dc.contributor.author | Tse, Brian W.C. | en_AU |
dc.contributor.author | Devilée, Lynn | en_AU |
dc.contributor.author | Voges, Holly K. | en_AU |
dc.contributor.author | Reynolds, Liam T. | en_AU |
dc.contributor.author | Krumeich, Sophie | en_AU |
dc.contributor.author | Mathieson, Ellen | en_AU |
dc.contributor.author | Abu-Bonsrah, Dad | en_AU |
dc.contributor.author | Karavendzas, Kathy | en_AU |
dc.contributor.author | Griffen, Brendan | en_AU |
dc.contributor.author | Titmarsh, Drew | en_AU |
dc.contributor.author | Elliott, David A. | en_AU |
dc.contributor.author | McMahon, James | en_AU |
dc.contributor.author | Suhrbier, Andreas | en_AU |
dc.contributor.author | Subbarao, Kanta | en_AU |
dc.contributor.author | Porrello, Enzo R. | en_AU |
dc.contributor.author | Smyth, Mark J. | en_AU |
dc.contributor.author | Engwerda, Christian R. | en_AU |
dc.contributor.author | MacDonald, Kelli PA. | en_AU |
dc.contributor.author | Bald, Tobias | en_AU |
dc.contributor.author | James, David E. | en_AU |
dc.contributor.author | Hudson, James E. | en_AU |
dc.date.accessioned | 2021-04-06T00:55:29Z | |
dc.date.available | 2021-04-06T00:55:29Z | |
dc.date.issued | 2021 | |
dc.identifier.uri | https://hdl.handle.net/2123/24826 | |
dc.description.abstract | 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. | en_AU |
dc.language.iso | en | en_AU |
dc.subject | COVID-19 | en_AU |
dc.subject | Coronavirus | en_AU |
dc.title | BET Inhibition Blocks Inflammation-Induced Cardiac Dysfunction and SARS-CoV-2 Infection | en_AU |
dc.type | Article | en_AU |
dc.identifier.doi | 10.1016/j.cell.2021.03.026 | |
dc.relation.arc | ||
dc.relation.nhmrc | ||
dc.relation.other | DFG | en_AU |
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