Regulation of the sodium-phosphate cotransporter Pit-1 and its role in vascular calcification.
Vascular calcification is caused by the deposition of basic calcium phosphate crystals in blood vessels, myocardium, and/or cardiac valves. Calcification decreases artery wall compliance, and arterial calcification is associated to mortality in hyperphosphatemic renal failure and diabetes mellitus. The calcification of the tunica media characterizes the arteriosclerosis observed with age, diabetes and end stage-renal disease, and it can develop independently from intima calcification. As part of the vascular calcification mechanism, vascular smooth muscle cells (VSMC) experience a transition from a contractile to an osteochondrogenic phenotype and a sequence of molecular events that are typical of endochondral ossification. The current evidence indicates a key role of increased phosphate uptake by VSMC for calcification, which supplies the substrate for hydroxyapatite formation and could trigger or potentiate VSMC transdiferentiation. The present review analyzes the sodium-phosphate cotransporter Pit-1, which is implicated in calcification. On the basis of the available data obtained in the study of vascular and osteoblastic experimental models, we discuss potential regulatory mechanisms that could lead to increased sodium-dependent phosphate uptake in vascular calcification.
Gonzalez
Magdalena
M
Instituto de Ciencias Biomédicas, Centro Estudios Moleculares de la Célula and Millenium Nucleus on Immunology and Immunotherapy, Universidad de Chile, Santiago 8389100, Chile.
Martínez
Rafael
R
Amador
Cristián
C
Michea
Luis
L
D000818:Animals; D001808:Blood Vessels / Q000378:metabolism* / Q000473:pathology; D002113:Calcification, Physiologic / Q000502:physiology*; D002118:Calcium / Q000378:metabolism; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins / Q000502:physiology; D009131:Muscle, Smooth, Vascular / Q000378:metabolism / Q000473:pathology; D010710:Phosphates / Q000378:metabolism*; D012964:Sodium / Q000378:metabolism*; D050611:Sodium-Phosphate Cotransporter Proteins, Type III / Q000378:metabolism*
D036341:Intercellular Signaling Peptides and Proteins; D010710:Phosphates; D050611:Sodium-Phosphate Cotransporter Proteins, Type III; D012964:Sodium; D002118:Calcium