Oxalate, a Potential Atherogenic Toxin of Uremia, Inhibits Endothelial Proliferation Induced by Heparin-binding Growth Factors In Vitro

Uremia, when treated with chronic dialysis, accelerates atherogenesis and its attendant complications. Using a chronic exposure model in vitro, it has previously been shown that uremic concentrations of oxalic acid inhibit endothelial cell (EC) proliferation and migration. In this paper the permeability of ECs to oxalate and the effect of oxalate on the proliferation of ECs stimulated by heparin-binding growth factors are studied. ECs were permeable to [14C]oxalate with uptake dependent on external oxalate concentration and efflux dependent on temperature, time, and external oxalate concentration (all P < 0.0001). The proliferation of unstimulated cultures and cultures stimulated with basic fibroblast growth factor (bFGF), endothelial cell growth supplement, α endothelial cell growth factor and β endothelial cell growth factor was inhibited by exposure to oxalate in all experiments from 14 to 100% in 14 to 60 d (N=19, all P < 0.001). Furthermore, surviving cultures were converted from the proliferative to...