Atherogenic concentrations of native low-density lipoproteins down-regulate nitric-oxide-synthase mRNA and protein levels in endothelial cells.
Atherogenic concentrations of native low-density lipoproteins down-regulate nitric-oxide-synthase mRNA and protein levels in endothelial cells.
复制标题
DOI：
10.1046/j.1432-1327.1998.2520378.x
复制
发表时间：
1998-03
期刊：
影响因子：
--
通讯作者：
F. Vidal;C. Colomé;J. Martínez-González;L. Badimón
中科院分区：
文献类型：
--
作者：
F. Vidal;C. Colomé;J. Martínez-González;L. Badimón
一氧化氮合酶蛋白家族是哺乳动物中代谢L-精氨酸形成一氧化氮（NO）的独特酶。低密度脂蛋白（LDL）的致动脉粥样硬化作用可能部分是通过其对内皮源性一氧化氮的作用介导的。为了确定天然LDL（nLDL）在致动脉粥样硬化浓度下是否能够调节NO合酶表达，我们用浓度递增的人nLDL（0-240 mg胆固醇/dl）处理人脐静脉内皮细胞不同时间段（2-48 h）。北方和Western印迹分析表明，内皮NO合酶mRNA和蛋白质下调致动脉粥样硬化浓度的nLDL（180和240毫克胆固醇/分升）后，48小时的孵育。放线菌酮和放线菌素D的实验表明，这种下调作用在转录水平。此外，在人体生理浓度（45 mg胆固醇/dl）下，用高密度脂蛋白处理细胞似乎不会改变内皮NO合酶的表达，这似乎表明nLDL通过特定的浓度依赖性机制影响基因转录速率。这些发现可能具有重要意义，因为它们提供了一种新的机制，高胆固醇血症诱导内皮细胞的早期变化，可能在动脉粥样硬化过程中具有病理生理学意义。
The nitric oxide synthase family of proteins is the unique class of mammalian enzymes that metabolizes L-arginine to form nitric oxide (NO). The atherogenic action of low-density lipoproteins (LDL) may be mediated, in part, by its effects on endothelial-derived nitric oxide. To determine whether native LDL (nLDL), at atherogenic concentrations, are capable of modulating NO synthase expression, we treated human umbilical vein endothelial cells with increasing concentrations of human nLDL (0-240 mg cholesterol/dl) for various time periods (2-48 h). Northern and western blot analyses indicate that both endothelial NO-synthase mRNA and protein are down-regulated by atherogenic concentrations of nLDL (180 and 240 mg cholesterol/dl) after 48 h of incubation. Cycloheximide and actinomycin D experiments suggest that this down-regulation operates at a transcriptional level. Additionally, treatment of the cells with high-density lipoproteins, at human physiological concentrations (45 mg cholesterol/dl), does not appear to alter the expression of endothelial NO synthase which seems to indicate that nLDL affect the gene transcription rate by a specific and concentration-dependent mechanism. These findings may have important implications because they provide a novel mechanism by which hypercholesterolemia induces early changes on endothelial cells that could have pathophysiological significance in the atherosclerotic process.