¹Department of Bioengineering, University of Washington, Seattle, Washington, USA

Correspondence: Cecilia M. Giachelli, Department of Bioengineering, Box 355061, University of Washington, Seattle, WA 98195, USA. E-mail: ceci@u.washington.edu

Received 22 July 2008; Revised 10 October 2008; Accepted 21 October 2008; Published online 14 January 2009.

Abstract

Vascular calcification is recognized as a major contributor to cardiovascular disease (CVD) in end stage renal disease (ESRD) patients. Susceptibility to vascular calcification is genetically determined and actively regulated by diverse inducers and inhibitors. One of these inducers, hyperphosphatemia, promotes vascular calcification and is a nontraditional risk factor for CVD mortality in ESRD patients. Vascular smooth muscle cells (SMCs) respond to elevated phosphate levels by undergoing an osteochondrogenic phenotype change and mineralizing their extracellular matrix through a mechanism requiring sodium-dependent phosphate cotransporters. Disease states and cytokines can increase expression of sodium-dependent phosphate cotransporters in SMCs, thereby increasing susceptibility to calcification even at phosphate concentrations that are in the normal range.