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Abstract: TH-PO516

Intravenous FGF-23 Loading Exacerbates Heart Failure with Preserved Ejection Fraction

Session Information

Category: Bone and Mineral Metabolism

  • 401 Bone and Mineral Metabolism: Basic

Authors

  • Saito, Tomohiro, Showa University School of Medicine, Yokohama, Japan
  • Mizobuchi, Masahide, Showa University School of Medicine, Yokohama, Japan
  • Shikida, Yasuto, Showa University School of Medicine, Yokohama, Japan
  • Kato, Tadashi, Showa University School of Medicine, Yokohama, Japan
  • Ogata, Hiroaki, Showa University School of Medicine, Yokohama, Japan
  • Koiwa, Fumihiko, Showa University School of Medicine, Yokohama, Japan
  • Akizawa, Tadao, Showa University School of Medicine, Yokohama, Japan
Background

The fact that FGF23 has an association with cardiovascular disease raises the question of whether it may not only be a biomarker of altered mineral metabolism and cardiovascular disease, but a therapeutic target. Herein, we studied the effect of continuous intravenous loading of FGF23 on mice of heart failure with preserved ejection fraction (HFpEF) model.

Methods

We used the deoxycorticosterone acetate (DOCA)-salt mouse model, which demonstrates mild hypertension and HFpEF. At the post-DOCA implantation day 7 mice were divided into two groups that received vehicle (DOCA+V) or FGF23 (DOCA+F) solution intravenously via a microinfusion pump for 10 days. Wild type mice were used as a control.

Results

Serum creatinine levels were comparable between the DOCA+F and the DOCA+V. Serum phosphorus levels were slightly increased in the DOCA+V compared with the control, whereas the levels remained normal in the DOCA+F. Serum FGF23 levels were slightly increased in the DOCA+V (249 pg/ml) compared with the control (51 pg/ml) and this increase was further amplified in the DOCA+F (1416 pg/ml). The heart weights were equal and significantly increased in the DOCA+V and the DOCA+F compared with the control. The DOCA+V (EF, 56%, E/A 1.0) showed HFpEF pattern, which was exacerbated in the DOCA+F (EF, 52%, E/A 0.7) assessed by echocardiography. Cardiac type I and type III collagen mRNA expressions were significantly increased in the DOCA+F compared with the control. Myocardial diameter was comparable between the DOCA+V (0.27 µm) and the DOCA+F (0.26 µm), whereas cardiac fibrosis was obvious in the DOCA+F (13,2 %) compared with the DOCA+V (7.0 %).

Conclusion

These results suggest that extremely high FGF23 levels have a crucial role in cardiac fibrosis which exacerbates HFpEF.