FGF23 impairs peripheral microvascular function in renal failure

American Journal of Physiology. Heart and Circulatory Physiology
Melissa VerkaikNIGRAM Consortium

Abstract

Cardiovascular diseases account for ~50% of mortality in patients with chronic kidney disease (CKD). Fibroblast growth factor 23 (FGF23) is independently associated with endothelial dysfunction and cardiovascular mortality. We hypothesized that CKD impairs microvascular endothelial function and that this can be attributed to FGF23. Mice were subjected to partial nephrectomy (5/6Nx) or sham surgery. To evaluate the functional role of FGF23, non-CKD mice received FGF23 injections and CKD mice received FGF23-blocking antibodies after 5/6Nx surgery. To examine microvascular function, myocardial perfusion in vivo and vascular function of gracilis resistance arteries ex vivo were assessed in mice. 5/6Nx surgery blunted ex vivo vasodilator responses to acetylcholine, whereas responses to sodium nitroprusside or endothelin were normal. In vivo FGF23 injections in non-CKD mice mimicked this endothelial defect, and FGF23 antibodies in 5/6Nx mice prevented endothelial dysfunction. Stimulation of microvascular endothelial cells with FGF23 in vitro did not induce ERK phosphorylation. Increased plasma asymmetric dimethylarginine concentrations were increased by FGF23 and strongly correlated with endothelial dysfunction. Increased FGF23 conce...Continue Reading

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Citations

May 10, 2019·Nephrology, Dialysis, Transplantation : Official Publication of the European Dialysis and Transplant Association - European Renal Association·Marc Vila CuencaMarc G Vervloet
Apr 9, 2020·Toxins·Thomas EbertPeter Stenvinkel
Dec 6, 2018·Nature Reviews. Nephrology·Marc Vervloet
Apr 3, 2020·Advances in Therapy·Mariano Rodríguez
Jan 9, 2021·Clinical Science·Jakob VoelklCarsten A Wagner
Mar 23, 2021·Frontiers in Cell and Developmental Biology·Chao ZhouXiongzhong Ruan

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Methods Mentioned

BETA
ELISA
dissection
scraping

Software Mentioned

PowerLab
MATLAB

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