FGF23 induces left ventricular hypertrophy.

Journal Article

Chronic kidney disease (CKD) is a public health epidemic that increases risk of death due to cardiovascular disease. Left ventricular hypertrophy (LVH) is an important mechanism of cardiovascular disease in individuals with CKD. Elevated levels of FGF23 have been linked to greater risks of LVH and mortality in patients with CKD, but whether these risks represent causal effects of FGF23 is unknown. Here, we report that elevated FGF23 levels are independently associated with LVH in a large, racially diverse CKD cohort. FGF23 caused pathological hypertrophy of isolated rat cardiomyocytes via FGF receptor-dependent activation of the calcineurin-NFAT signaling pathway, but this effect was independent of klotho, the coreceptor for FGF23 in the kidney and parathyroid glands. Intramyocardial or intravenous injection of FGF23 in wild-type mice resulted in LVH, and klotho-deficient mice demonstrated elevated FGF23 levels and LVH. In an established animal model of CKD, treatment with an FGF-receptor blocker attenuated LVH, although no change in blood pressure was observed. These results unveil a klotho-independent, causal role for FGF23 in the pathogenesis of LVH and suggest that chronically elevated FGF23 levels contribute directly to high rates of LVH and mortality in individuals with CKD.

Full Text

Duke Authors

Cited Authors

  • Faul, C; Amaral, AP; Oskouei, B; Hu, M-C; Sloan, A; Isakova, T; Gutiérrez, OM; Aguillon-Prada, R; Lincoln, J; Hare, JM; Mundel, P; Morales, A; Scialla, J; Fischer, M; Soliman, EZ; Chen, J; Go, AS; Rosas, SE; Nessel, L; Townsend, RR; Feldman, HI; St John Sutton, M; Ojo, A; Gadegbeku, C; Di Marco, GS; Reuter, S; Kentrup, D; Tiemann, K; Brand, M; Hill, JA; Moe, OW; Kuro-O, M; Kusek, JW; Keane, MG; Wolf, M

Published Date

  • November 2011

Published In

Volume / Issue

  • 121 / 11

Start / End Page

  • 4393 - 4408

PubMed ID

  • 21985788

Electronic International Standard Serial Number (EISSN)

  • 1558-8238

International Standard Serial Number (ISSN)

  • 1558-8238

Digital Object Identifier (DOI)

  • 10.1172/jci46122

Language

  • eng