title: Vascular calcification: in vitro evidence for the role of inorganic phosphate.
abstract: Uremic patients are prone to widespread ectopic extraskeletal calcification resulting from an imbalance of systemic inorganic phosphate (Pi). There can be serious consequences of this process, particularly when it results in the calcification of the vasculature. A recent study examined the response of cultured human aortic smooth muscle cells to varying levels of extracellular Pi. Cells that were exposed to Pi levels similar to those seen in uremic patients (>1.4 mmol/L) showed dose-dependent increases in cell culture calcium deposition. The results of this study also defined the role of elevated phosphate in transforming the vascular phenotype of these cells to an osteogenic phenotype, such that a predisposition for calcification was created. Pi-induced changes included increased expression of the osteogenic markers osteocalcin and core-binding factor-1 genes, the latter of which is considered a "master gene" critical for osteoblast differentiation. These changes occur early after exposure to high phosphate levels and seem to be mediated by a sodium-dependent phosphate co-transporter, Pit-1 (Glvr-1). Calcification of vascular cells also seems to occur in the absence of a mineral imbalance but in the presence of platelet-derived growth factor, a potent atherogenic factor. Taken together, these data suggest that calcification of vascular cells can occur early in a phosphate-rich environment similar to that seen in patients with renal failure and in a platelet-derived growth factor-rich atherosclerotic region under normal phosphorus conditions. From a clinical viewpoint, it seems that early control or prevention of hyperphosphatemia may reduce coronary calcification and its associated morbidity and mortality for patients on dialysis.
authors.affiliation: Bioengineering Department, University of Washington, Seattle, Washington 98194-1720, USA. ceci@u.washington.edu
authors.forename: Cecilia M
authors.initials: CM
authors.lastname: Giachelli
mesh_terms: D002114:Calcinosis / Q000209:etiology* / Q000378:metabolism*; D002352:Carrier Proteins / Q000378:metabolism; D002478:Cells, Cultured; D006801:Humans; D008565:Membrane Proteins / Q000378:metabolism; D009131:Muscle, Smooth, Vascular / Q000378:metabolism* / Q000473:pathology; D010710:Phosphates / Q000378:metabolism*; D049294:Phospholipid Transfer Proteins; D010982:Platelet-Derived Growth Factor / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D014652:Vascular Diseases / Q000209:etiology* / Q000378:metabolism* / Q000473:pathology
chemical_list: D002352:Carrier Proteins; D008565:Membrane Proteins; D010710:Phosphates; D049294:Phospholipid Transfer Proteins; D010982:Platelet-Derived Growth Factor; D012333:RNA, Messenger