Show simple item record

FGF23/FGFR4-mediated left ventricular hypertrophy is reversible.

dc.contributor.author Grabner, Alexander
dc.contributor.author Wolf, Myles
dc.contributor.author Schramm, Karla
dc.contributor.author Silswal, Neerupma
dc.contributor.author Hendrix, Matt
dc.contributor.author Yanucil, Christopher
dc.contributor.author Czaya, Brian
dc.contributor.author Singh, Saurav
dc.contributor.author Hermann, Sven
dc.contributor.author Stypmann, Jörg
dc.contributor.author Di Marco, Giovana Seno
dc.contributor.author Brand, Marcus
dc.contributor.author Wacker, Michael J
dc.contributor.author Faul, Christian
dc.date.accessioned 2019-05-01T15:01:07Z
dc.date.available 2019-05-01T15:01:07Z
dc.date.issued 2017-05-16
dc.identifier 10.1038/s41598-017-02068-6
dc.identifier.issn 2045-2322
dc.identifier.issn 2045-2322
dc.identifier.uri https://hdl.handle.net/10161/18484
dc.description.abstract 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.
dc.language eng
dc.publisher Springer Nature
dc.relation.ispartof Scientific reports
dc.relation.isversionof 10.1038/s41598-017-02068-6
dc.subject Myocytes, Cardiac
dc.subject Animals
dc.subject Mice, Knockout
dc.subject Mice
dc.subject Rats
dc.subject Hypertrophy, Left Ventricular
dc.subject Disease Models, Animal
dc.subject Fibroblast Growth Factors
dc.subject Biopsy
dc.subject Diet
dc.subject Signal Transduction
dc.subject Myocardial Contraction
dc.subject Receptor, Fibroblast Growth Factor, Type 4
dc.title FGF23/FGFR4-mediated left ventricular hypertrophy is reversible.
dc.type Journal article
dc.date.updated 2019-05-01T15:01:04Z
pubs.begin-page 1993
pubs.issue 1
pubs.organisational-group School of Medicine
pubs.organisational-group Duke
pubs.organisational-group Medicine, Nephrology
pubs.organisational-group Medicine
pubs.organisational-group Clinical Science Departments
pubs.organisational-group Duke Clinical Research Institute
pubs.organisational-group Institutes and Centers
pubs.organisational-group Population Health Sciences
pubs.organisational-group Basic Science Departments
pubs.publication-status Published
pubs.volume 7
duke.contributor.orcid Grabner, Alexander|0000-0002-5544-1896


Files in this item

Thumbnail

This item appears in the following Collection(s)

Show simple item record