Myeloperoxidase impacts vascular function by altering perivascular adipocytes’ secretome and phenotype in obesity
Obesity, a main driver of cardiovascular morbidity, contributes to endothelial dysfunction and inflammation in adipose tissues. Perivascular adipose tissue (PVAT) surrounds arteries and influences vascular function. In obesity, immune cells, including myeloperoxidase (MPO)-releasing myeloid cells, accumulate in PVAT. In this study, we show MPO levels to correlate with body weight and endothelial function in obese patients (n = 33) and mice. In addition, MPO deficiency reduces immune cell frequency, enhances PVAT beiging via soluble guanylyl cyclase β1 (sGC-β1), and increases oxygen consumption in vivo. Further, nitrotyrosine formation and inflammatory cytokine release are attenuated in obese Mpo<sup>-/-</sup> mice. Mechanistically, adiponectin (APN) secretion improves endothelial function and reduces arterial stiffness. In vitro, MPO-treated human white adipocytes show lower APN and brown adipocyte marker expression but increased inflammation. Thus, MPO impairs vascular function via PVAT inflammation and suppression of vasoprotective mediators, making it a potential therapeutic target in obesity-related cardiovascular disease.
Authors
- Max Landerer
- Holger Winkels (ORCID: https://orcid.org/0000-0003-1333-2031)
- Friedrich Felix Hoyer
- Simon Braumann (ORCID: https://orcid.org/0000-0002-9969-6073)
- Raphael Herzog (ORCID: https://orcid.org/0009-0002-5764-3990)
- Harshal Nemade (ORCID: https://orcid.org/0000-0002-2704-181X)
- Philipp Peitsmeyer
- Jens Alber
- Simon Geißen (ORCID: https://orcid.org/0000-0002-7835-4111)
- Maysam Ahdab
- Staffan Hildebrand (ORCID: https://orcid.org/0000-0003-1889-907X)
- Felix Sebastian Nettersheim (ORCID: https://orcid.org/0000-0002-4090-3357)
- Dennis Mehrkens (ORCID: https://orcid.org/0000-0002-8578-0290)
- Stephan Baldus
- Martin Mollenhauer (ORCID: https://orcid.org/0000-0002-3220-9269)
- Philipp von Stein (ORCID: https://orcid.org/0000-0003-4548-3897)
- Alexander Hof (ORCID: https://orcid.org/0000-0001-6554-8892)
- Henning Guthoff (ORCID: https://orcid.org/0000-0002-0979-1190)
- Regina Braun
- Felix S.R. Picard (ORCID: https://orcid.org/0000-0001-7624-4704)
- Jasper Schäkel
- Matti Adam
- Jens C. Brüning (ORCID: https://orcid.org/0000-0002-6619-0092)
- Alexander Pfeifer
Institutions
- University of Bonn (DE)
- Universität Hamburg (DE)
- University of Cologne (DE)
- University Hospital Bonn (DE)
- Max Planck Institute for Metabolism Research (DE)
- University Hospital Cologne (DE)
Publication Details
- Journal
- Cell Reports Medicine
- Published
- 2025-04-18
- DOI
- https://doi.org/10.1016/j.xcrm.2025.102087
- Citations
- 3
- Primary Topic
- Cardiovascular Disease and Adiposity
- Type
- article
- Field-Weighted Citation Impact
- 4.16