Characterization of phosphate transport in rat vascular smooth muscle cells: implications for vascular calcification.
OBJECTIVE
Hyperphosphatemia and inorganic phosphate (Pi) transport by vascular smooth muscle cells (VSMCs) have been implicated in the pathogenesis of vascular calcification. The aim of this work has been to characterize Pi transport in VSMCs.


RESULTS
Primary cultures of VSMCs express both high affinity Na-dependent and Na-independent components of Pi transport. Under physiological conditions both transport systems are saturated, show similar activity, and are inhibited by increasing pH. The Na-dependent transport is also weakly inhibited by phosphonoformic acid (PFA) (3.9 mmol/L IC50 at 0.05 mmol/L Pi). Real-time polymerase chain reaction shows that Pit1 and Pit2 are expressed to the same degree, and no other Pi transporters are significantly expressed. When expressed in Xenopus oocytes they are strictly Na-dependent, with high affinities for Pi, and are inhibited by increasing pH, but only weakly inhibited by PFA. We have used RNA interference to demonstrate that Pit1 and Pit2 are the transporters responsible for Na-dependent Pi transport in VSMCs.


CONCLUSIONS
Taken together these novel findings suggest new roles of Pi transport in the pathogenesis of VC and have implications as potential future clinical targets.
Villa-Bellosta
Ricardo
R
Laboratory of Molecular Toxicology, University of Zaragoza, Spain.
Bogaert
Yolanda E
YE
Levi
Moshe
M
Sorribas
Víctor
V
D000818:Animals; D002114:Calcinosis / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D005260:Female; D017245:Foscarnet / Q000494:pharmacology; D006863:Hydrogen-Ion Concentration; D017136:Ion Transport / Q000187:drug effects / Q000235:genetics; D009131:Muscle, Smooth, Vascular / Q000378:metabolism* / Q000473:pathology; D009865:Oocytes / Q000378:metabolism; D016133:Polymerase Chain Reaction; D012313:RNA / Q000235:genetics* / Q000378:metabolism; D051381:Rats; D018894:Reverse Transcriptase Inhibitors / Q000494:pharmacology; D050611:Sodium-Phosphate Cotransporter Proteins, Type III / Q000096:biosynthesis / Q000235:genetics*; D050598:Vesicular Glutamate Transport Protein 1 / Q000096:biosynthesis / Q000235:genetics; D014982:Xenopus laevis
D018894:Reverse Transcriptase Inhibitors; C493588:Slc20a1 protein, rat; D050611:Sodium-Phosphate Cotransporter Proteins, Type III; D050598:Vesicular Glutamate Transport Protein 1; D017245:Foscarnet; D012313:RNA