FGF23/FGFR4-mediated left ventricular hypertrophy is reversible.

Published

Journal Article

Fibroblast growth factor (FGF) 23 is a phosphaturic hormone that directly targets cardiac myocytes via FGF receptor (FGFR) 4 thereby inducing hypertrophic myocyte growth and the development of left ventricular hypertrophy (LVH) in rodents. Serum FGF23 levels are highly elevated in patients with chronic kidney disease (CKD), and it is likely that FGF23 directly contributes to the high rates of LVH and cardiac death in CKD. It is currently unknown if the cardiac effects of FGF23 are solely pathological, or if they potentially can be reversed. Here, we report that FGF23-induced cardiac hypertrophy is reversible in vitro and in vivo upon removal of the hypertrophic stimulus. Specific blockade of FGFR4 attenuates established LVH in the 5/6 nephrectomy rat model of CKD. Since CKD mimics a form of accelerated cardiovascular aging, we also studied age-related cardiac remodeling. We show that aging mice lacking FGFR4 are protected from LVH. Finally, FGF23 increases cardiac contractility via FGFR4, while known effects of FGF23 on aortic relaxation do not require FGFR4. Taken together, our data highlight a role of FGF23/FGFR4 signaling in the regulation of cardiac remodeling and function, and indicate that pharmacological interference with cardiac FGF23/FGFR4 signaling might protect from CKD- and age-related LVH.

Full Text

Duke Authors

Cited Authors

  • Grabner, A; Schramm, K; Silswal, N; Hendrix, M; Yanucil, C; Czaya, B; Singh, S; Wolf, M; Hermann, S; Stypmann, J; Di Marco, GS; Brand, M; Wacker, MJ; Faul, C

Published Date

  • May 16, 2017

Published In

Volume / Issue

  • 7 / 1

Start / End Page

  • 1993 -

PubMed ID

  • 28512310

Pubmed Central ID

  • 28512310

Electronic International Standard Serial Number (EISSN)

  • 2045-2322

International Standard Serial Number (ISSN)

  • 2045-2322

Digital Object Identifier (DOI)

  • 10.1038/s41598-017-02068-6

Language

  • eng