High Intakes of Bioavailable Phosphate May Promote Systemic Oxidative Stress and Vascular Calcification by Boosting Mitochondrial Membrane Potential—Is Good Magnesium Status an Antidote?

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Chronic kidney disease is characterized by markedly increased risk for cardiovascular
mortality, vascular calcification, and ventricular hypertrophy, and is associated with increased
systemic oxidative stress. Hyperphosphatemia, reflecting diminished glomerular phosphate (Pi)
clearance, coupled with a compensatory increase in fibroblast growth factor 23 (FGF23) secretion
are thought to be key mediators of this risk. Elevated serum and dietary Pi and elevated plasma
FGF23 are associated with increased cardiovascular and total mortality in people with normal
baseline renal function. FGF23 may mediate some of this risk by promoting cardiac hypertrophy
via activation of fibroblast growth factor receptor 4 on cardiomyocytes. Elevated serum Pi can
also cause a profound increase in systemic oxidative stress, and this may reflect the ability of Pi to
act directly on mitochondria to boost membrane potential and thereby increase respiratory chain
superoxide production. Moreover, elevated FGF23 likewise induces oxidative stress in vascular
endothelium via activation of NADPH oxidase complexes. In vitro exposure of vascular smooth
muscle cells to elevated Pi provokes an osteoblastic phenotypic transition that is mediated by
increased mitochondrial oxidant production; this is offset dose-dependently by increased exposure
to magnesium (Mg). In vivo, dietary Mg is protective in rodent models of vascular calcification. It is
proposed that increased intracellular Mg opposes Pi’s ability to increase mitochondrial membrane
potential; this model could explain its utility for prevention of vascular calcification and predicts
that Mg may have a more global protective impact with regard to the direct pathogenic effects
of hyperphosphatemia.
Idioma originalInglés
Número de artículo1744
Páginas (desde-hasta)1-8
Número de páginas8
EstadoPublicada - 9 jul. 2021

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