RT Journal Article
T1 The direct effect of fibroblast growth factor 23 on vascular smooth muscle cell phenotype and function.
A1 Vergara, Noemi
A1 de Mier, M Victoria Pendon-Ruiz
A1 Rodelo-Haad, Cristian
A1 Revilla-Gonzalez, Gonzalo
A1 Membrives, Cristina
A1 Diaz-Tocados, Juan M
A1 Martinez-Moreno, Julio M
A1 Torralbo, Ana I
A1 Herencia, Carmen
A1 Rodriguez-Ortiz, Maria Encarnacion
A1 Lopez-Baltanas, Rodrigo
A1 Richards, Williams G
A1 Felsenfeld, Arnold
A1 Almaden, Yolanda
A1 Martin-Malo, Alejandro
A1 Ureña, Juan
A1 Santamaria, Rafael
A1 Soriano, Sagrario
A1 Rodriguez, Mariano
A1 Muñoz-Castañeda, Juan R
K1 FGF23
K1 Arterial stiffness
K1 Chronic kidney disease
K1 MicroRNA
K1 Vascular smooth muscle cells
AB In chronic kidney disease (CKD) patients, increased levels of fibroblast growth factor 23 (FGF23) are associated with cardiovascular mortality. The relationship between FGF23 and heart hypertrophy has been documented, however, it is not known whether FGF23 has an effect on vasculature. Vascular smooth muscle cells VSMCs may exhibit different phenotypes; our hypothesis is that FGF23 favours a switch from a contractile to synthetic phenotype that may cause vascular dysfunction. Our objective was to determine whether FGF23 may directly control a change in VSMC phenotype. This study includes in vitro, in vivo and ex vivo experiments and evaluation of patients with CKD stages 2-3 studying a relationship between FGF23 and vascular dysfunction. In vitro studies show that high levels of FGF23, by acting on its specific receptor FGFR1 and Erk1/2, causes a change in the phenotype of VSMCs from contractile to synthetic. This change is mediated by a downregulation of miR-221/222, which augments the expression of MAP3K2 and PAK1. miR-221/222 transfections recovered the contractile phenotype of VSMCs. Infusion of recombinant FGF23 to rats increased vascular wall thickness, with VSMCs showing a synthetic phenotype with a reduction of miR-221 expression. Ex-vivo studies on aortic rings demonstrate also that high FGF23 increases arterial stiffening. In CKD 2-3 patients, elevation of FGF23 was associated with increased pulse wave velocity and reduced plasma levels of miR-221/222. In VSMCs, high levels of FGF23, through the downregulation of miR-221/222, causes a change to a synthetic phenotype. This change in VSMCs increases arterial stiffening and impairs vascular function, which might ultimately worsen cardiovascular disease.
PB Oxford University Press
YR 2022
FD 2022
LK http://hdl.handle.net/10668/19820
UL http://hdl.handle.net/10668/19820
LA en
NO Vergara N, de Mier MVP, Rodelo-Haad C, Revilla-González G, Membrives C, Díaz-Tocados JM, et al. The direct effect of fibroblast growth factor 23 on vascular smooth muscle cell phenotype and function. Nephrol Dial Transplant. 2023 Feb 13;38(2):322-343
DS RISalud
RD Apr 19, 2025