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 plasma 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 [3H]thymidine, [3H]mevalonolactone or 45Ca(2+) to determine how the plasma from the patients influences cell growth and function. We found that less [3H]thymidine (P<0.05), less [3H]mevalonolactone (P<0.05) and more 45Ca(2+) (P<0.001) was incorporated into ECs cultured in the plasma from 36 patients with 83+/-4% stenosis than from the 36 controls. When synthetic 7beta-hydroxycholesterol, cholesterol 5beta,6beta-epoxide, cholesterol 5alpha,6alpha-epoxide and 7-ketocholesterol were added to the plasma from the controls, the influx of 45Ca(2+) into ECs then equaled that in the plasma of patients. The enhanced incorporation of 45Ca(2+) into the ECs cultured in the plasma both from the patients and from controls with added synthetic oxysterols substantiates in vitro the hypothesis that oxysterols increase the influx of calcium into cells. These data indicated that an excess of oxysterols in the plasma of the patients was cytotoxic to the cultured cells.