An excess concentration of oxysterols in the plasma is cytotoxic to cultured endothelial cells

To test if there is an excess concentration of oxysterols in the plasma of the patients with cardiovascular disease, we analyzed the oxysterol content in the plasma from 105 cardiac catheterized patients with angina and 80 +/ - 8% stenosis in their coronary arteries. The result showed that the plasma contained a significantly higher concentration of oxysterols than did plas ma from 105 age- and sex-matched, non-catheterized and angina-free controls (P < 0.05). We used endothelial cells (ECs) cultured in medium containing either [H-3]thymidine, [H-3]mevalonolactone or Ca-45(2+) to determine how t he plasma from the patients influences cell growth and function. We found t hat less [H-3]thymidine (P < 0.05), less [H-3]mevalonolactone (P < 0.05) an d more Ca-45(2+) (P < 0.001) was incorporated into ECs cultured in the plas ma from 36 patients with 83 +/- 4% stenosis than from the 36 controls. When synthetic 7 beta-hydroxycholesterol, cholesterol 5 alpha,6 alpha-epoxide, cholesterol 5 alpha,6 alpha-epoxide and 7-ketocholesterol were added to the plasma from the controls, the influx of Ca-45(2+) into ECs then equaled th at in the plasma of patients. The enhanced incorporation of Ca-45(2+) into the ECs cultured in the plasma both from the patients and from controls wit h added synthetic oxysterols substantiates in vitro the hypothesis that oxy sterols increase the influx of calcium into cells. These data indicated tha t an excess of oxysterols in the plasma of the patients was cytotoxic to th e cultured cells. (C) 2000 Elsevier Science Ireland Ltd. All rights reserve d.