Abstract: TH-PO0014
FTO-Mediated m6A Demethylation of ANKRD1 Drives Vascular Calcification by Antagonizing YTHDF1-Mediated mRNA Decay
Session Information
- Mineral Balance: Physiology and Pathophysiology
October 22, 2026 | Location: Exhibit Hall A, Convention Center
Abstract Time: 10:00 AM - 12:00 PM
Category: Bone and Mineral Metabolism
- 501 Bone and Mineral Metabolism: Basic
Authors
- Lin, Tingru, Peking University People's Hospital, Beijing, China
- Zuo, Li, Peking University People's Hospital, Beijing, China
Background
Vascular calcification is a major cardiovascular complication of chronic kidney disease and is closely associated with increased cardiovascular morbidity and mortality. N6-methyladenosine RNA modification has emerged as an important regulator of cardiovascular disease.
Methods
Human aortic vascular smooth muscle cells were cultured in high-phosphate calcifying medium to induce osteogenic differentiation in vitro. A 5/6 nephrectomy rat model was used to establish CKD-associated VC in vivo.
Results
FTO expression was significantly increased in calcified HAVSMCs, aortic tissues from CKD rats, and iliac artery tissues from patients with CKD, accompanied by reduced global m6A levels. Pharmacological inhibition of FTO with FB23-2 significantly attenuated vascular calcification in vitro and in vivo. Mechanistically, FTO antagonized YTH N6-methyladenosine RNA binding protein 1 (YTHDF1)-mediated ANKRD1 mRNA decay. Functional experiments further demonstrated that ANKRD1 promoted osteogenic differentiation of vascular smooth muscle cells and activated extracellular signal-regulated kinase signaling.
Conclusion
FTO promotes CKD-associated vascular calcification through m6A-dependent stabilization of ANKRD1 mRNA by antagonizing YTHDF1-mediated transcript decay and activating ERK signaling.
Figure 1. FTO is upregulated during CKD-associated vascular calcification and is accompanied by reduced global m6A levels.
Graphical abstrcat
Funding
- Government Support – Non-U.S.