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Cardiovascular Disease I
Title
Cardiovascular Disease I
Editor
iConcept Press
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USD$109.99
ISBN
978-1-922227-54-6
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Chapter 4

Cardiovascular Disease I

Implications of the Phosphate Regulatory FGF-23/Klotho System in Cardiovascular Disease

by Javier Donate-Correa, Ernesto Martín-Núñez, Mercedes Muros de Fuentes, Carmen Mora-Fernández and Juan F. Navarro-González

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Abstract

Derangements in phosphorous homeostasis are involved in multiple physiopathologic mechanisms and clinical processes. These alterations are very frequent in chronic kidney disease (CKD) patients, in whom phosphorous retention and hyperphosphatemia are common features that partially explain the high car-diovascular morbidity and mortality observed. However, not only variations in phosphate but also in phosphate-regulatory factors, have been linked with morbidity and mortality, suggesting that both could be related to cardiovascular adverse outcomes including atherosclerosis, arterial calcification, vascular stiffness, and left ventricular hypertrophy (LVH). Variations in components of phosphate regulatory system traditionally associated with increased cardio-vascular risk are low vitamin D and high parathyroid hormone (PTH) levels. However, the recently ap-pearing of a novel phosphatemic central regulator: the fibroblast growth factor (FGF) 23/Klotho system, not only has changed our understanding of mineral metabolism regulation, but has also provided several novel relationships between phosphate imbalance and increased cardiovascular risk. Nowadays, FGF23 is considered as the principal regulator of phosphatemia. This bone-derived hormone induces phosphaturia and inhibits calcitriol synthesis in the kidney, therefore maintaining systemic phos-phate homeostasis. FGF23 belongs to the so-called endocrine FGFs, characterised for requiring a co-factor to bind and activate its cognate receptors. Specifically, FGF23 requires Klotho, a single-pass transmembrane protein, to exert its phosphaturic actions. Expression of Klotho gene has determines the tissue-specific signalling of FGF23 and has been described in renal tubules, parathyroid glands, choroid plexus, and, recently, in human vascular tissue. A soluble form of Klotho can be also detected in blood, urine, and cerebrospinal fluid and appears to have diverse endocrine actions. Diverse studies point to the potential roles of FGF23 excess in cardiovascular disease (CVD) incidence in patients with and without kidney impairment, including increased mortality risk, LVH, vascular dysfunc-tion, atherosclerosis and cardiovascular events. Moreover, several works have confirmed diverse Klotho not FGF23-related favourable mechanisms over the vascular system, including calcitriol and nitric oxide synthesis, suppression of Wnt signalling, oxidative stress, and vascular calcifications. The existence of a soluble form and the recently described expression in human vascular tissue and vascular smooth muscle cells (VSMCs) of Klotho may partially explain these effects over the cardiovascular system. Currently, the potential utility of these proteins as biomarkers is an area of intense investigation especially focused in renal patients. Several studies point to its usefulness as unprecedented biomarkers for, but no exclusively, nephrologists. However, there is a long way to go in which FGF23 and Klotho will have to prove its usefulness in the early diagnosis and its prognostic value in CVD.

Author Details

Javier Donate-Correa
Research Unit, University Hospital Nuestra Señora de Candelaria, Santa Cruz de Tenerife, Spain, Spain
Ernesto Martín-Núñez
Research Unit, University Hospital Nuestra Señora de Candelaria, Santa Cruz de Tenerife, Spain, Spain
Mercedes Muros de Fuentes
Clinical Analysis Service, University Hospital Nuestra Señora de Candelaria, Santa Cruz de Tenerife, Spain, Spain
Carmen Mora-Fernández
Research Unit, University Hospital Nuestra Señora de Candelaria, Santa Cruz de Tenerife, Spain, Spain
Juan F. Navarro-González
Research Unit and Nephrology Service, University Hospital Nuestra Señora de Candelaria, Santa Cruz de Tenerife, Spain, Spain

Citation

Javier Donate-Correa, Ernesto Martín-Núñez, Mercedes Muros de Fuentes, Carmen Mora-Fernández and Juan F. Navarro-González. Implications of the Phosphate Regulatory FGF-23/Klotho System in Cardiovascular Disease. In Cardiovascular Disease I. ISBN:978-1-922227-54-6. iConcept Press. 2014.

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