José Alberto Navarro-García1, María Fernández-Velasco2, Carmen Delgado3, Juan F Delgado4, Makoto Kuro-O5, Luis M Ruilope1,6,7, Gema Ruiz-Hurtado1. 1. Cardiorenal Translational Laboratory, Institute of Research i+12, Hospital Universitario de Octubre/CIBERCV, Madrid, Spain. 2. IdiPAZ Institute for Health Research/CIBERCV, Madrid, Spain. 3. Biomedical Research Institute Alberto Sols/CIBERCV, Madrid, Spain. 4. Cardiology Service, Hospital Universitario 12 de Octubre/CIBERCV, Madrid, Spain. 5. Division of Anti-aging Medicine, Center for Molecular Medicine, Jichi Medical University, Shimotsuke, Tochigi, Japan. 6. Department of Preventive Medicine and Public Health, School of Medicine, Universidad Autónoma de Madrid, Madrid, Spain. 7. European University of Madrid, Madrid, Spain.
Abstract
BACKGROUND: Profound disturbances in mineral metabolism are closely linked to the progression of chronic kidney disease. However, increasing clinical and experimental evidence indicates that alterations in phosphate homoeostasis could have an even stronger impact on the heart. AIM: The aim of this review is to provide the reader with an update of how alterations in mineral metabolism are related to direct and indirect cardiotoxic effects beyond the nephrology setting. RESULTS: Evidence exists that alterations in mineral metabolism that are related to changes in parathyroid hormone (PTH), vitamin D, and the FGF-23-klotho axis have direct pathological consequences for the heart. Alterations in plasma PTH levels are associated with cardiac dysfunction and detrimental cardiac remodelling. Several clinical studies have associated vitamin D deficiency with the prevalence of cardiovascular disease (CV) and its risk factors. Recent evidences support deleterious direct and nonphosphaturic effects of FGF-23 on the heart as hypertrophy development. In contrast, reduced systemic klotho levels are related to CV damage, at least when advanced age is present. In addition, we discuss how these mineral metabolism molecules can counteract each other in some situations, in the context of failed clinical trials on cardiac protection as is the case of vitamin D supplementation. CONCLUSIONS: Among all mineral components, an increase in systemic FGF-23 levels is considered to have the greatest CV impact and risk. However, it is quite possible that many intracellular mechanisms mediated by FGF-23, especially those related to cardiomyocyte function, remain to be discovered.
BACKGROUND: Profound disturbances in mineral metabolism are closely linked to the progression of chronic kidney disease. However, increasing clinical and experimental evidence indicates that alterations in phosphate homoeostasis could have an even stronger impact on the heart. AIM: The aim of this review is to provide the reader with an update of how alterations in mineral metabolism are related to direct and indirect cardiotoxic effects beyond the nephrology setting. RESULTS: Evidence exists that alterations in mineral metabolism that are related to changes in parathyroid hormone (PTH), vitamin D, and the FGF-23-klotho axis have direct pathological consequences for the heart. Alterations in plasma PTH levels are associated with cardiac dysfunction and detrimental cardiac remodelling. Several clinical studies have associated vitamin D deficiency with the prevalence of cardiovascular disease (CV) and its risk factors. Recent evidences support deleterious direct and nonphosphaturic effects of FGF-23 on the heart as hypertrophy development. In contrast, reduced systemic klotho levels are related to CV damage, at least when advanced age is present. In addition, we discuss how these mineral metabolism molecules can counteract each other in some situations, in the context of failed clinical trials on cardiac protection as is the case of vitamin D supplementation. CONCLUSIONS: Among all mineral components, an increase in systemic FGF-23 levels is considered to have the greatest CV impact and risk. However, it is quite possible that many intracellular mechanisms mediated by FGF-23, especially those related to cardiomyocyte function, remain to be discovered.
Authors: Marta Gil-Fernández; José Alberto Navarro-García; Almudena Val-Blasco; Laura González-Lafuente; José Carlos Martínez; Angélica Rueda; Maria Tamayo; José Luis Morgado; Carlos Zaragoza; Luis Miguel Ruilope; Carmen Delgado; Gema Ruiz-Hurtado; María Fernández-Velasco Journal: Int J Mol Sci Date: 2020-11-23 Impact factor: 5.923
Authors: Carolina Victoria Cruz Junho; Laura González-Lafuente; José Alberto Navarro-García; Elena Rodríguez-Sánchez; Marcela Sorelli Carneiro-Ramos; Gema Ruiz-Hurtado Journal: Int J Mol Sci Date: 2022-02-18 Impact factor: 5.923
Authors: Agata Zdanowicz; Szymon Urban; Barbara Ponikowska; Gracjan Iwanek; Robert Zymliński; Piotr Ponikowski; Jan Biegus Journal: J Pers Med Date: 2022-05-29