Holland J A, Pritchard K A, Rogers N J, Stemerman M B
Department of Medicine, New York Medical College, Valhalla 10595.
Am J Pathol. 1988 Sep;132(3):474-8.
Cultured human umbilical vein endothelial cells (EC) exposed to atherogenic levels of low density lipoprotein (LDL) for protracted periods demonstrated no measurable evidence of overt cytotoxicity, but were perturbed as indicated by an increase in prostacyclin (PGI2) production. Confluent EC were incubated with high LDL concentrations (240 or 330 mg/dl cholesterol) for 1 to 12 days. LDL was added to culture media containing 25% human lipoprotein-deficient serum to determine the effects of LDL independent of other lipoproteins. LDL did not injure EC as assessed by cell count, vital dye exclusion, 51chromium release, and lactate dehydrogenase release. Although high concentrations of LDL did not cause EC cytotoxicity, such LDL concentrations did results in increased PGI2 generation. PGI2 accumulation in postincubation media was increased two-to-fivefold in otherwise unstimulated cells as measured by radioimmunoassay of the stable PGI2 breakdown product, 6-keto-PGF1-alpha. This elevation persisted for the entire 12-day exposure to high LDL concentrations. These results indicate that prolonged exposure to atherogenic concentrations of LDL does not effect EC viability, but does cause an endothelial perturbation as demonstrated by an increased PGI2 production.
长时间暴露于致动脉粥样硬化水平的低密度脂蛋白（LDL）的培养人脐静脉内皮细胞（EC）未显示出明显细胞毒性的可测量证据，但如前列环素（PGI2）产生增加所示，细胞受到了干扰。将汇合的内皮细胞与高浓度LDL（240或330mg/dl胆固醇）孵育1至12天。将LDL添加到含有25%人脂蛋白缺乏血清的培养基中，以确定LDL独立于其他脂蛋白的作用。通过细胞计数、活性染料排除、51铬释放和乳酸脱氢酶释放评估，LDL未损伤内皮细胞。尽管高浓度LDL未引起内皮细胞毒性，但这种LDL浓度确实导致PGI2生成增加。通过对稳定的PGI2分解产物6-酮-PGF1-α进行放射免疫测定，在未受刺激的细胞中，孵育后培养基中的PGI2积累增加了2至5倍。在整个12天暴露于高浓度LDL期间，这种升高持续存在。这些结果表明，长时间暴露于致动脉粥样硬化浓度的LDL不会影响内皮细胞活力，但会如PGI2产生增加所示引起内皮细胞干扰。
