ArticleNephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association2017
Vitamin D treatment attenuates cardiac FGF23/FGFR4 signaling and hypertrophy in uremic rats.
Article in Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 45 papers.
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Who cites it
45 citing papers in PubMed, 86 citations in OpenAlex.
- Broken signals: when the mineralostat alters the cardiovascular system.Pediatric nephrology (Berlin, Germany) · 2026Review
- High-Phosphate-Induced Hypertension: The Pathogenic Role of Fibroblast Growth Factor 23 (FGF23) Signaling in Sympathetic Nervous System Activation.International journal of molecular sciences · 2026Review
- Current Controversies on Adequate Circulating Vitamin D Levels in CKD.International journal of molecular sciences · 2025Review
- High Dietary Phosphate Intake Induces Hypertension and Sympathetic Overactivation via Central Fibroblast Growth Factor Receptor Signaling.Circulation · 2025Article
- Office Blood Pressure and Obesity in Children with X-Linked Hypophosphatemia.Calcified tissue international · 2025Observational
- Emerging concepts on the FGF23 regulation and activity.Molecular and cellular biochemistry · 2025Review
- Assessment of the Relationship Between Serum Vitamin D Level and Its Cardiovascular Outcomes: A Systematic Review and Meta-analysis Study.Journal of the Saudi Heart Association · 2025Review
- Fibroblast Growth Factor 23 and Risk of Heart Failure Subtype: The CRIC (Chronic Renal Insufficiency Cohort) Study.Kidney medicine · 2023Article
- Review
- Direct and indirect effects of fibroblast growth factor 23 on the heart.Frontiers in endocrinology · 2023Review
- Indoxyl sulfate induces left ventricular hypertrophyFrontiers in cardiovascular medicine · 2023Article
- Strategies to lower fibroblast growth factor 23 bioactivity.Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association · 2022Article
- Shedding Light on the Complex Regulation of FGF23.Metabolites · 2022Review
- Article
- High FGF23 Levels Failed to Predict Cardiac Hypertrophy in Animal Models of Hyperphosphatemia and Chronic Renal Failure.Journal of the Endocrine Society · 2021Article
- Phosphate and fibroblast growth factor 23 in diabetes.Clinical science (London, England : 1979) · 2021Review
- Mortality in Hemodialysis Patients with COVID-19, the Effect of Paricalcitol or Calcimimetics.Nutrients · 2021Observational
- Fibroblast growth factor 23 (FGF23) induces ventricular arrhythmias and prolongs QTc interval in mice in an FGF receptor 4-dependent manner.American journal of physiology. Heart and circulatory physiology · 2021Article
- Review
- Vitamin D Effects on Bone Homeostasis and Cardiovascular System in Patients with Chronic Kidney Disease and Renal Transplant Recipients.Nutrients · 2021Review
Corrections and comments
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Authors and funding
9 authors at 3 institutions in 2 countries.
Funding
Abstract
backgroundVitamin D deficiency and excess of circulating fibroblast growth factor 23 (FGF23) contribute to cardiovascular mortality in patients with chronic kidney disease (CKD). FGF23 activates FGF receptor 4 and (FGFR4) calcineurin/nuclear factor of activated T cells (NFAT) signaling in cardiac myocytes, thereby causing left ventricular hypertrophy (LVH). Here, we determined if 1,25-dihydroxyvitamin D (calcitriol) inhibits FGF23-induced cardiac signaling and LVH.
methods5/6 nephrectomized (5/6 Nx) rats were treated with different doses of calcitriol for 4 or 10 weeks and cardiac expression of FGF23/FGFR4 and activation of calcineurin/NFAT as well as LVH were analyzed. FGFR4 activation and hypertrophic cell growth were studied in cultured cardiac myocytes that were co-treated with FGF23 and calcitriol.
resultsIn 5/6Nx rats with LVH, we detected elevated FGF23 expression in bone and myocardium, increased cardiac expression of FGFR4 and elevated cardiac activation of calcineurin/NFAT signaling. Cardiac expression levels of FGF23 and FGFR4 significantly correlated with the presence of LVH in uremic rats. Treatment with calcitriol reduced LVH as well as cardiac FGFR4 expression and calcineurin/NFAT activation. Bone and cardiac FGF23 expression were further stimulated by calcitriol in a dose-dependent manner, but levels of intact cardiac FGF23 protein were suppressed by high-dose calcitriol. In cultured cardiac myocytes, co-treatment with calcitriol blocked FGF23-induced activation of FGFR4 and hypertrophic cell growth.
conclusionsOur data suggest that in CKD, cardioprotective effects of calcitriol stem from its inhibitory actions on the cardiac FGF23/FGFR4 system, and based on their counterbalancing effects on cardiac myocytes, high FGF23 and low calcitriol synergistically contribute to cardiac hypertrophy.
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