Fibroblast Growth Factor 23 Exacerbates Cardiac Fibrosis in Deoxycorticosterone Acetate-Salt Mice With Hypertension

Fibroblast growth factor 23 (FGF23) is associated with cardiovascular disease in patients with chronic kidney disease; however, the mechanisms underlying the effect of FGF23 on cardiac function remain to be investigated. Herein, we studied the effect of continuous intravenous (CIV) FGF23 loading in a deoxycorticosterone acetate (DOCA)-salt mouse model with mild chronic kidney disease and hypertension as well as heart failure with a preserved ejection fraction. Wild-type male mice were randomly allocated to 4 groups: normal control, vehicle-treated DOCA-salt mice, FGF23-treated DOCA-salt mice, and FGF23- and calcitriol-treated DOCA-salt mice. The DOCA-salt mice received the agents via the CIV route for 10 days using an infusion minipump. DOCA-salt mice that received FGF23 showed a marked increase in the serum FGF23 level, and echocardiography in these mice revealed heart failure with a preserved ejection fraction. These mice also showed exacerbation of myocardial fibrosis, concomitant with an inverse and significant correlation with Cyp27b1 expression. Calcitriol treatment attenuated FGF23-induced cardiac fibrosis and improved diastolic function via inhibition of transforming growth factor-β signaling. This effect was independent of the systemic and local levels of FGF23. These results suggest that CIV FGF23 loading exacerbates cardiac fibrosis and that locally abnormal vitamin D metabolism is involved in this mechanism. Calcitriol attenuates this exacerbation by mediating transforming growth factor-β signaling independently of the FGF23 levels.

 

Comments：

FGF23 is associated with cardiovascular disease in chronic kidney disease patients, but its effect on cardiac function is unknown; this study showed that continuous intravenous FGF23 loading in a mouse model with mild chronic kidney disease and heart failure with a preserved ejection fraction worsened myocardial fibrosis, which was prevented by calcitriol treatment by inhibiting transforming growth factor-β signaling independently of FGF23 levels.

Related Products

Cat.No.	Product Name	Information
S1466	Calcitriol	Calcitriol is a nonselective vitamin D receptor activator/agonist(VDRA), exhibiting a 10-fold higher vitamin D receptor (VDR) binding affinity(IC50=0.4 nM) than the selective VDRA paricalcitol. Solutions are unstable and should be fresh-prepared.

Related Targets

Vitamin