1-Phosphatidylinositol 3-Phosphate 5-Kinase Inhibition by Apilimod Promotes an Adipocyte-Like Vascular Smooth Muscle Cell Phenotype and Prevents Arterial Calcification
Pharmacological inhibition of PIKFYVE disrupts YAP-TEAD signaling, thereby reducing arterial calcification by limiting the calcification potential of EVs and suppressing osteogenic SMC programming, but also induces an adipocyte-like SMC phenotype with lipid accumulation. These findings emphasize the need to consider SMC phenotypic plasticity and potential adverse effects when developing therapeutic strategies for arterial calcification.
Authors
- Andreas Edsfeldt (ORCID: https://orcid.org/0000-0002-2691-9192)
- Claudia Goettsch (ORCID: https://orcid.org/0000-0002-7973-1329)
- Guillaume Falgayrac (ORCID: https://orcid.org/0000-0003-1806-1509)
- A Rauch
- B Mir
- Ljubica Matic (ORCID: https://orcid.org/0000-0002-7294-9667)
- Jiangming Sun (ORCID: https://orcid.org/0000-0001-6814-1297)
- Jessica Thiel (ORCID: https://orcid.org/0009-0005-7143-9023)
- Martina Rauner (ORCID: https://orcid.org/0000-0002-4067-6799)
- N Hense
- Ulf Hedin (ORCID: https://orcid.org/0000-0001-9212-3945)
- Mirna Barsoum (ORCID: https://orcid.org/0000-0003-0838-8137)
- Maria Alejandra Ramirez-Torres
- I Goncalves
- Christian Preisinger
- Andrea Gogels
- Nikolaus Marx
- Emiel P.C. van der Vorst
- Sikander Hayat
- Heidi Noels
- Mara Terliesner
Institutions
- Karolinska University Hospital (SE)
- University of Southern Denmark (DK)
- Lund University (SE)
- Odense University Hospital (DK)
- Université du littoral côte d'opale (FR)
- Centre Hospitalier Universitaire de Lille (FR)
- Wallenberg Wood Science Center (SE)
- Skåne University Hospital (SE)
- University Hospital Carl Gustav Carus (DE)
- Technische Universität Dresden (DE)
- Ludwig-Maximilians-Universität München (DE)
- RWTH Aachen University (DE)
Publication Details
- Journal
- Circulation Research
- Published
- 2026-01-14
- DOI
- https://doi.org/10.1161/circresaha.125.326772
- Primary Topic
- Parathyroid Disorders and Treatments
- Type
- article
- Field-Weighted Citation Impact
- 0.00