Transient Inhibition of Translation Improves Cardiac Function After Ischemia/Reperfusion by Attenuating the Inflammatory Response
Global protein synthesis is inhibited during ischemia and shortly after reperfusion, followed by a recovery of protein synthesis that exceeds baseline levels in the border and infarct zones. Activation of mRNA translation after reperfusion is driven by mTORC1/eIF4F-mediated regulation of initiation and mediates an mRNA network that controls inflammation and monocyte infiltration to the myocardium. Transient inhibition of the mTORC1-/eIF4F axis inhibits translation and attenuates Ly6C<sup>hi</sup> monocyte infiltration by inhibiting a proinflammatory response at the site of injury and of circulating monocytes.
Authors
- Daniel Finke (ORCID: https://orcid.org/0000-0002-0536-7536)
- Tobias Jakobi (ORCID: https://orcid.org/0000-0002-3906-0401)
- Norbert Frey (ORCID: https://orcid.org/0000-0001-7611-378X)
- Arica Beisaw
- Christoph P. Hofmann (ORCID: https://orcid.org/0000-0002-3389-6582)
- Mirko Völkers (ORCID: https://orcid.org/0000-0003-2344-1856)
- Verena Kamuf‐Schenk
- Fereshteh S. Younesi (ORCID: https://orcid.org/0000-0002-8024-4296)
- Ellen Malovrh (ORCID: https://orcid.org/0000-0003-0911-6125)
- Hugo A. Katus (ORCID: https://orcid.org/0000-0002-2293-2314)
- Etienne Boileau (ORCID: https://orcid.org/0000-0001-9355-0973)
- Johannes Fischer (ORCID: https://orcid.org/0000-0003-1499-6163)
- Frank Stein (ORCID: https://orcid.org/0000-0001-9695-1692)
- Florian Leuschner (ORCID: https://orcid.org/0000-0003-1157-474X)
- Claudia Stroh
- Ole M. Schwerdt
- Mandy Rettel (ORCID: https://orcid.org/0000-0002-8304-3385)
- Adrian Serafin
- Clara Sandmann (ORCID: https://orcid.org/0000-0001-9115-8628)
- Nikole J. Byrne (ORCID: https://orcid.org/0000-0002-0006-7147)
- Heiko Bugger (ORCID: https://orcid.org/0000-0002-3524-0405)
- Zoe Löwenthal
- Ingmar S. Meyer
- Florian Sicklinger
- Lonny Jürgensen
Institutions
- University of Arizona (US)
- University of Phoenix (US)
- Medical University of Graz (AT)
- Heidelberg University (DE)
- University Hospital Heidelberg (DE)
- German Center for Infection Research (DE)
- European Molecular Biology Laboratory (DE)
- Norwegian Womens Public Health Association (NO)
Publication Details
- Journal
- Circulation
- Published
- 2024-08-29
- DOI
- https://doi.org/10.1161/circulationaha.123.067479
- Citations
- 21
- Primary Topic
- Cardiac Ischemia and Reperfusion
- Type
- article
- Field-Weighted Citation Impact
- 8.92