CD14 Blockade Modulates Macrophage-Mediated Immunological Injury in a Translational Model of Reperfused ST-Segment Elevation Myocardial Infarction
These preclinical trials provide the first evidence of cluster of differentiation 14 (CD14) blockade with a murine analogue of atibuclimab, a CD14-neutralizing antibody, preventing secondary immunological exacerbation of cardiac injury in a translational mouse model of reperfused ST-segment elevation myocardial infarction (STEMI), assessed using multiple clinical modalities. Multiomic studies suggest CD14 blockade downregulated macrophage-specific proinflammatory and tissue-wide remodeling processes without suppression of monocyte-macrophage infiltration or repair. These findings support a clinically practicable targeted immunomodulatory strategy of CD14 blockade initiated at reperfusion to prevent chronic immunological progression toward ischemic heart failure, and provide new insights into the pleiotropic roles of CD14 in inflammation and myocardial injury.
Authors
- Junedh Amrute (ORCID: https://orcid.org/0000-0002-6851-0168)
- Alexander R. Pinto (ORCID: https://orcid.org/0000-0001-6421-4970)
- David M. Kaye (ORCID: https://orcid.org/0000-0003-4058-0372)
- Kory J. Lavine (ORCID: https://orcid.org/0000-0003-1948-9945)
- Angela Vais
- Chad Johnson (ORCID: https://orcid.org/0000-0002-0017-4284)
- Brian W. Ziegelaar
- Haoyun Fang (ORCID: https://orcid.org/0000-0001-6582-1975)
- Mark W. Appleby
- Helen Kiriazis (ORCID: https://orcid.org/0009-0009-6658-1489)
- Stéphanie Jansen (ORCID: https://orcid.org/0000-0002-4623-5070)
- Ian C. Hsu (ORCID: https://orcid.org/0000-0003-2782-9997)
- David W. Greening (ORCID: https://orcid.org/0000-0001-7516-485X)
- Anita C. Thomas (ORCID: https://orcid.org/0000-0002-3792-2653)
- Gabriella E. Farrugia (ORCID: https://orcid.org/0000-0002-9240-9027)
- David Crowe
- Jason Bloom (ORCID: https://orcid.org/0000-0001-8838-0332)
- Malathi S.I. Dona
- Crisdion Krstevski (ORCID: https://orcid.org/0000-0001-8408-7331)
- Adam Parslow (ORCID: https://orcid.org/0000-0002-9868-6914)
- Camilla Cohen
- Garry Redlich
- Antonio Abbate (ORCID: https://orcid.org/0000-0002-1930-785X)
- Julie R. McMullen (ORCID: https://orcid.org/0000-0002-8316-1066)
- Yow Keat Tham (ORCID: https://orcid.org/0000-0002-9790-1926)
- D. Donner (ORCID: https://orcid.org/0000-0003-4924-720X)
- Jonathan Noonan (ORCID: https://orcid.org/0000-0001-9173-0903)
- Waled Shihata (ORCID: https://orcid.org/0000-0002-5737-0737)
- Bing H. Wang (ORCID: https://orcid.org/0000-0001-9580-2548)
- Guy Y. Krippner (ORCID: https://orcid.org/0000-0003-0885-5217)
- David Wright (ORCID: https://orcid.org/0000-0002-7535-8651)
- Natalia Carvajal
- K. Grigolon (ORCID: https://orcid.org/0009-0006-9324-5673)
- Andrew Brown (ORCID: https://orcid.org/0000-0003-2918-634X)
- S. Loh
Institutions
- Baker Heart and Diabetes Institute (AU)
- La Trobe University (AU)
- Washington University in St. Louis (US)
- Blaze Bioscience (United States) (US)
- Monash Health (AU)
- Alfred Health (AU)
- University of Virginia (US)
- Monash University (AU)
Publication Details
- Journal
- JACC Basic to Translational Science
- Published
- 2025-10-23
- DOI
- https://doi.org/10.1016/j.jacbts.2025.101393
- Primary Topic
- Cardiac Fibrosis and Remodeling
- Type
- article
- Field-Weighted Citation Impact
- 0.00