A possible antiatherogenic role for phosphocitrate through modulation of low density lipoprotein uptake and degradation in aortic smooth muscle cells.
The present study reports the influence of a phosphorylated polycarboxylic acid, phosphocitrate, on low density lipoprotein (LDL) metabolism in cultured rabbit aortic smooth muscle cells. Phosphocitrate profoundly influenced both LDL binding and degradation. At the maximal effective concentration (2 mM), phosphocitrate released approximately 90% of the receptor-bound [125I]LDL whilst the total amount of [125I]LDL degraded was reduced by 60%. Measurement of total cholesterol accumulation revealed that even in the presence of high concentrations of added LDL, phosphocitrate (2 mM) diminished cholesterol levels close to the basal levels seen in incubations in lipoprotein-deficient serum. Further, this inhibitory effect of phosphocitrate was demonstrable after 24 h at 37 degrees C. Phosphocitrate, a recognized anticalcifying agent, possesses a strong negative charge to size ratio at physiological pH. It is postulated that the observed effects probably arise from charge interference and/or its ability to modulate cellular calcium concentration.
D000818:Animals; D001011:Aorta / Q000166:cytology* / Q000378:metabolism; D001161:Arteriosclerosis / Q000517:prevention & control*; D002478:Cells, Cultured; D002784:Cholesterol / Q000097:blood; D002951:Citrates / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D007457:Iodine Radioisotopes; D008077:Lipoproteins, LDL / Q000378:metabolism*; D009131:Muscle, Smooth, Vascular / Q000166:cytology / Q000187:drug effects / Q000378:metabolism* / Q000648:ultrastructure; D011817:Rabbits; D011956:Receptors, Cell Surface / Q000187:drug effects / Q000502:physiology; D018110:Receptors, Lipoprotein; D013997:Time Factors
D002951:Citrates; D007457:Iodine Radioisotopes; D008077:Lipoproteins, LDL; D011956:Receptors, Cell Surface; D018110:Receptors, Lipoprotein; C014148:phosphocitrate; D002784:Cholesterol