Asset Details
Do you wish to reserve the book?
FGF23-Mediated Activation of Local RAAS Promotes Cardiac Hypertrophy and Fibrosis
Hey, we have placed the reservation for you!
By the way, why not check out events that you can attend while you pick your title.
Oops! Something went wrong.
Looks like we were not able to place the reservation. Kindly try again later.
Are you sure you want to remove the book from the shelf?
FGF23-Mediated Activation of Local RAAS Promotes Cardiac Hypertrophy and Fibrosis
Do you wish to request the book?
FGF23-Mediated Activation of Local RAAS Promotes Cardiac Hypertrophy and Fibrosis
Please be aware that the book you have requested cannot be checked out. If you would like to checkout this book, you can reserve another copy
We have requested the book for you!
Your request is successful and it will be processed during the Library working hours. Please check the status of your request in My Requests.
Oops! Something went wrong.
Looks like we were not able to place your request. Kindly try again later.
Journal Article
FGF23-Mediated Activation of Local RAAS Promotes Cardiac Hypertrophy and Fibrosis
2019
Overview
Patients with chronic kidney disease (CKD) are prone to developing cardiac hypertrophy and fibrosis, which is associated with increased fibroblast growth factor 23 (FGF23) serum levels. Elevated circulating FGF23 was shown to induce left ventricular hypertrophy (LVH) via the calcineurin/NFAT pathway and contributed to cardiac fibrosis by stimulation of profibrotic factors. We hypothesized that FGF23 may also stimulate the local renin–angiotensin–aldosterone system (RAAS) in the heart, thereby further promoting the progression of FGF23-mediated cardiac pathologies. We evaluated LVH and fibrosis in association with cardiac FGF23 and activation of RAAS in heart tissue of 5/6 nephrectomized (5/6Nx) rats compared to sham-operated animals followed by in vitro studies with isolated neonatal rat ventricular myocytes and fibroblast (NRVM, NRCF), respectively. Uremic rats showed enhanced cardiomyocyte size and cardiac fibrosis compared with sham. The cardiac expression of Fgf23 and RAAS genes were increased in 5/6Nx rats and correlated with the degree of cardiac fibrosis. In NRVM and NRCF, FGF23 stimulated the expression of RAAS genes and induced Ngal indicating mineralocorticoid receptor activation. The FGF23-mediated hypertrophic growth of NRVM and induction of NFAT target genes were attenuated by cyclosporine A, losartan and spironolactone. In NRCF, FGF23 induced Tgfb and Ctgf, which were suppressed by losartan and spironolactone, only. Our data suggest that FGF23-mediated activation of local RAAS in the heart promotes cardiac hypertrophy and fibrosis.
Publisher
MDPI AG,MDPI
Subject
/ Enzymes
/ Fibroblast Growth Factors - metabolism
/ Fibrosis
/ Heart
/ Heart Ventricles - metabolism
/ Heart Ventricles - pathology
/ Hypertrophy, Left Ventricular - etiology
/ Hypertrophy, Left Ventricular - metabolism
/ Hypertrophy, Left Ventricular - pathology
/ Male
/ Myocytes, Cardiac - pathology
/ Peptides
/ Renal Insufficiency, Chronic - complications
/ Renal Insufficiency, Chronic - metabolism
