Atherogenesis. Mitigation of monocyte adhesion to arterial endothelium in hyperlipidemic rats by phosphocitrate, a phosphorylated polycarboxylic acid.

Phosphocitrate, a phosphorylated polycarboxylic acid ameliorates two early events in atherogenesis. When administered to rats on an atherosclerotic diet (112 mumol/kg body wt./day), it reduced monocyte adhesion to aortic endothelium from 34 +/- 7 cells/HPF for untreated rats to 1 +/- 1 cell/HPF, a value seen in normal, non-atherosclerotic rats. Transmission electron microscopy of aortic sections showed no evidence of subendothelial lipid accumulation in phosphocitrate-treated rats despite the high circulating plasma lipid levels. The mechanisms of action of phosphocitrate are unknown but the indications are that its influence may be mediated through its polyanionic chemical nature and/or its ability to modulate cellular calcium accumulation. In addition to its possible therapeutic value as an anti-calcifying and anti-atherogenic compound, phosphocitrate may prove useful as an experimental probe for studying the cellular basis of atherogenesis.