ASN's Mission

ASN leads the fight to prevent, treat, and cure kidney diseases throughout the world by educating health professionals and scientists, advancing research and innovation, communicating new knowledge, and advocating for the highest quality care for patients.

learn more

Contact ASN

1401 H St, NW, Ste 900, Washington, DC 20005

email@asn-online.org

202-640-4660

The Latest on Twitter

Kidney Week

Abstract: TH-PO512

Fibroblast Growth Factor 23 Produces Arterial Stiffness Through Changes in Vascular Smooth Muscle Cell Phenotype

Session Information

Category: Bone and Mineral Metabolism

  • 401 Bone and Mineral Metabolism: Basic

Authors

  • Munoz-Castaneda, Juan R., Instituto Maimonides de Investigacion Biomedica de Cordoba (IMIBIC), Cordoba, Spain
  • Rodriguez Ortiz, Maria Encarnacion, Instituto Maimonides de Investigacion Biomedica de Cordoba (IMIBIC), Cordoba, Spain
  • Vergara segura, Noemi, Instituto Maimonides de Investigacion Biomedica de Cordoba (IMIBIC), Cordoba, Spain
  • Pendon-Ruiz de Mier, Victoria, Hospital Universitario Reina Sofia, Cordoba, Spain
  • Rodelo-Haad, Cristian, Hospital Universitario Reina Sofia, Cordoba, Spain
  • Diaz Tocados, Juan M., Instituto Maimonides de Investigacion Biomedica de Cordoba (IMIBIC), Cordoba, Spain
  • Almaden peña, Yolanda, Unidad Investigacion.IMIBIC.Hospital Reina Sofia, Cordoba, Spain
  • Rodriguez, Mariano, Hospital Universitario Reina Sofia, Cordoba, Spain

Group or Team Name

  • GC13. Calcium Metabolism. VAscular Calcification group
Background

In patients with chronic kidney disease (CKD), high levels of c-terminal fibroblast growth factor 23 (FGF23) are associated with cardiovascular disease and mortality. Vascular smooth muscle cells (VSMC) may present two differentiated functional phenotypes, contractile and synthetic. An excess of synthetic VSMC has been associated with vascular dysfunctions. It is unknown whether FGF23 may promote phenotypic transition causing vascular stiffness.

Methods

The expression of VSMC markers, miR-221 and miR-222 was determined in VSMC treated with high recombinant FGF23. In vivo, the VSMC markers were analyzed in aorta of rats receiving recombinant FGF23 for 14 days. Furthermore, the relationship between FGF23 and arterial stiffness was investigated in CKD patients stages 2-3.

Results

High levels of FGF23 promoted VSMC transition from a contractile to a synthetic phenotype. These effects were mediated through FGFR1 and Erk1/2 phosphorylation. Inhibition of both pathways enhanced contractile phenotype of VSMC. The pro-contractile microRNAs miR-221 and miR-222 were reduced by FGF23 and miR-221 transfection recovered the contractile phenotype of VSMC decreased by FGF23. In rats, exogenous infusion of FGF23 increased tunica media thickness and promoted synthetic phenotype reducing plasma levels of miR-221. In a group of CKD 2-3 patients it was observed an association between FGF23 and pulse pressure, reflecting vascular stiffness together with low plasma levels of miR-221 and miR-222.

Conclusion

FGF23 favors the transition of VSMC from contractile to synthetic phenotype causing vascular dysfunction and arterial stiffness. This may be a mechanism by which FGF23 contribute directly to the development of vascular disease in CKD patients.

Funding

  • Government Support - Non-U.S.