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(Arteriosclerosis, Thrombosis, and Vascular Biology. 2007;27:1030.)
© 2007 American Heart Association, Inc.

Vascular Biology

Characterization of Phosphate Transport in Rat Vascular Smooth Muscle Cells

Implications for Vascular Calcification

Ricardo Villa-Bellosta; Yolanda E. Bogaert; Moshe Levi; Víctor Sorribas

From the Laboratory of Molecular Toxicology (R.V.-B., V.S.), University of Zaragoza, Spain; and the Departments of Medicine (Y.E.B., M.L.) and Physiology and Biophysics (M.L.), Division of Renal Diseases and Hypertension, Denver VAMC and University of Colorado at Denver and Health Sciences Center, Denver.

Correspondence to Víctor Sorribas, Laboratory of Molecular Toxicology, University of Zaragoza, Veterinary Faculty, Calle Miguel Servet 177, 50013 Zaragoza, Spain. E-mail sorribas{at}unizar.es

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.

Methods and 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.

Key Words: vascular calcification • phosphate transport • VSMC • Pit1 • Pit2

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