Open AccessHigh Fibroblast Growth Factor 23 concentrations in experimental renal failure impair calcium handling in cardiomyocytes
Author(s) -
Verkaik Melissa,
Oranje Maarten,
Abdurrachim Desiree,
Goebel Max,
Gam Zeineb,
Prompers Jeanine J.,
Helmes Michiel,
Wee Pieter M.,
Velden Jolanda,
Kuster Diederik W.,
Vervloet Marc G.,
Eringa Etto C.
Publication year - 2018
Publication title -
physiological reports
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.918
H-Index - 39
ISSN - 2051-817X
DOI - 10.14814/phy2.13591
Subject(s) - medicine , diastole , endocrinology , calcium , systole , kidney disease , fibroblast growth factor 23 , nephrectomy , heart failure , cardiology , kidney , ejection fraction , blood pressure , parathyroid hormone
The overwhelming majority of patients with chronic kidney disease ( CKD ) die prematurely before reaching end‐stage renal disease, mainly due to cardiovascular causes, of which heart failure is the predominant clinical presentation. We hypothesized that CKD ‐induced increases of plasma FGF 23 impair cardiac diastolic and systolic function. To test this, mice were subjected to 5/6 nephrectomy (5/6Nx) or were injected with FGF 23 for seven consecutive days. Six weeks after surgery, plasma FGF 23 was higher in 5/6Nx mice compared to sham mice (720 ± 31 vs. 256 ± 3 pg/mL, respectively, P = 0.034). In cardiomyocytes isolated from both 5/6Nx and FGF 23 injected animals the rise of cytosolic calcium during systole was slowed (−13% and −19%, respectively) as was the decay of cytosolic calcium during diastole (−15% and −21%, respectively) compared to controls. Furthermore, both groups had similarly decreased peak cytosolic calcium content during systole. Despite lower cytosolic calcium contents in CKD or FGF 23 pretreated animals, no changes were observed in contractile parameters of cardiomyocytes between the groups. Expression of calcium handling proteins and cardiac troponin I phosphorylation were similar between groups. Blood pressure, the heart weight:tibia length ratio, α ‐ MHC / β ‐ MHC ratio and ANF mRNA expression, and systolic and diastolic function as measured by MRI did not differ between groups. In conclusion, the rapid, CKD ‐induced rise in plasma FGF 23 and the similar decrease in cardiomyocyte calcium transients in modeled kidney disease and following 1‐week treatment with FGF 23 indicate that FGF 23 partly mediates cardiomyocyte dysfunction in CKD .