Oxalic acid alters intracellular calcium in endothelial cells.
Patients with chronic renal failure (CRF) who undergo hemodialysis experience accelerated atherosclerosis and premature death. While the cause of uremic atherogenesis is unknown, we reported that uremic levels of oxalate, an excretory metabolite, severely inhibit proliferation and migration of human endothelial cells (EC) without affecting other cell types. Since the physical, cellular and molecular events of endothelial injury are clearly established as key factors in the development of plaque, and since inhibition of proliferation and migration would enhance endothelial injury, we have proposed that oxalate is an atherogenic toxin of uremia. In the current study, we used in situ cell counting and total DNA measurement to show that the inhibitory effect of oxalate on proliferation is exclusive to endothelial cells among human cell lines tested (endothelial cells, fibroblasts, aortic smooth muscle cells (SMC), glioblastoma and embryonic kidney cells). Using the fluorescent calcium indicators fura-2 and fluo-3, we correlated the inhibition of proliferation with a prolonged elevation in intracellular free calcium levels. We also demonstrated that all cells tested internalize 14C-oxalic acid. We conclude that plasma oxalate exerts its atherogenic effects by elevating intracellular calcium exclusively in endothelial cells and preventing re-endothelialization.
Recht
Phoebe A
PA
Leon H. Charney Division of Cardiology, New York University School of Medicine, New York, NY, USA.
Tepedino
Gerard J
GJ
Siecke
Neil W
NW
Buckley
Michael T
MT
Mandeville
John T
JT
Maxfield
Frederick R
FR
Levin
Richard I
RI
D001693:Biological Transport, Active / Q000187:drug effects / Q000502:physiology; D002118:Calcium / Q000378:metabolism*; D002129:Calcium Oxalate / Q000494:pharmacology; D002455:Cell Division; D002478:Cells, Cultured; D042783:Endothelial Cells; D004730:Endothelium, Vascular / Q000166:cytology* / Q000187:drug effects* / Q000648:ultrastructure; D005347:Fibroblasts / Q000166:cytology; D005453:Fluorescence; D006801:Humans; D017136:Ion Transport / Q000187:drug effects*; D009131:Muscle, Smooth, Vascular / Q000166:cytology; D019815:Oxalic Acid / Q000494:pharmacology*; D011336:Probability; D012680:Sensitivity and Specificity; D014471:Umbilical Veins / Q000166:cytology
D002129:Calcium Oxalate; D019815:Oxalic Acid; D002118:Calcium