Targeting the pyruvate dehydrogenase kinase/pyruvate dehydrogenase axis modulates neutrophil and smooth muscle cell pathological responses and prevents abdominal aortic aneurysm formation
We show that the PDK/PDH axis is skewed in human AAA. Through the inhibition of PDK, in vitro and in vivo, we demonstrated that the PDK/PDH axis is a key regulator of vascular- and neutrophil-associated pathological responses with AAA formation. Our study pinpoints immunometabolic reprogramming using PDK inhibitors as an attractive strategy to fight AAA disease.
Authors
- Mikkel G. Terp (ORCID: https://orcid.org/0000-0002-4468-6900)
- Lars Melholt Rasmussen (ORCID: https://orcid.org/0000-0001-5795-4794)
- Lasse Bach Steffensen (ORCID: https://orcid.org/0000-0001-6353-4227)
- Daniel F.J. Ketelhuth (ORCID: https://orcid.org/0000-0002-0087-116X)
- Emilie Grupe
- Andrietta Grentzmann (ORCID: https://orcid.org/0000-0003-2007-8457)
- María J. Forteza (ORCID: https://orcid.org/0000-0003-4907-4783)
- Michelle Duen Nilsson (ORCID: https://orcid.org/0009-0007-6585-4022)
- Jes S. Lindholt (ORCID: https://orcid.org/0000-0001-9536-4488)
- Gustavo Luis Tripodi (ORCID: https://orcid.org/0000-0003-2620-6202)
- Maja Dembić (ORCID: https://orcid.org/0000-0003-2505-6863)
- Mark Burton (ORCID: https://orcid.org/0000-0002-3782-5933)
- Maria Sabater‐Lleal (ORCID: https://orcid.org/0000-0002-0128-379X)
- Silke Griepke
- Gerard Temprano‐Sagrera (ORCID: https://orcid.org/0000-0001-6136-8915)
- Pia Søe Jensen (ORCID: https://orcid.org/0000-0002-0116-722X)
- Hans Christian Beck (ORCID: https://orcid.org/0000-0002-7763-3637)
- Micaella Pereira da Fonseca (ORCID: https://orcid.org/0000-0002-0632-0668)
- Jane Stubbe (ORCID: https://orcid.org/0000-0002-2703-453X)
- Janne Fuglsang Hansen (ORCID: https://orcid.org/0009-0001-6610-1643)
- Mads Thomassen (ORCID: https://orcid.org/0000-0003-0078-1217)
- Yousef Tallouzi
Institutions
- University of Southern Denmark (DK)
- Odense University Hospital (DK)
- Hospital de Sant Pau (ES)
- Karolinska Institutet (SE)
- Centre for Biomedical Network Research on Rare Diseases (ES)
- Centro de Investigación Biomédica en Red (ES)
- Region of Southern Denmark (DK)
- BioClinicum (Russia) (RU)
- Institut de Recerca Sant Pau (ES)
Publication Details
- Journal
- Cardiovascular Research
- Published
- 2025-03-04
- DOI
- https://doi.org/10.1093/cvr/cvaf032
- Citations
- 6
- Primary Topic
- Macrophage Migration Inhibitory Factor
- Type
- article
- Field-Weighted Citation Impact
- 4.78
Funders
- Hjerteforeningen
- Fundació la Marató de TV3
- European Commission
- Novo Nordisk
- Syddansk Universitet
- Novo Nordisk Fonden
- Simon Fougner Hartmanns Familiefond
- HORIZON EUROPE Framework Programme
- Instituto de Salud Carlos III
- Agencia Estatal de Investigación
- European Social Fund