Institute of Clinical Medicine, National Yang-Ming University, Taipei, Taiwan.
J Nutr Biochem. 2012 May;23(5):458-68. doi: 10.1016/j.jnutbio.2011.01.011. Epub 2011 Jun 17.
Atherosclerosis is a chronic inflammatory disease of the vessel wall associated with oxidized low-density lipoprotein (oxLDL)-induced apoptosis of endothelial cells. Coenzyme Q10 (CoQ10), a potent antioxidant and a critical intermediate of the electron transport chain, has been reported to inhibit LDL oxidation and thus the progression of atherosclerosis. However, its molecular mechanisms on endothelial cells remain still unclarified.
In this study, primary human umbilical vein endothelial cell cultures treated with oxLDL were used to explore the protective effects of CoQ10.
Our results showed that CoQ10 attenuated the oxLDL-induced generation of reactive oxygen species and improved the antioxidant capacity. CoQ10 also attenuated the oxLDL-mediated down-regulation of endothelial nitric oxide synthase (eNOS) and up-regulation of inducible nitric oxide synthase (iNOS). In addition, CoQ10 suppressed oxLDL-activated NF-κB and downstream inflammatory mediators, including expression of adhesion molecules, release of proinflammatory cytokines and the adherence of monocytic THP-1 cells. Moreover, CoQ10 attenuated oxLDL-altered proapoptotic responses. The inhibitor of eNOS (L-NIO 10 μM) and iNOS (1400W 10 μM) as well as NO enhancer (SNP 10 μM) were used to clean up the mechanism.
These results provide new insight into the possible molecular mechanisms by which CoQ10 protects against atherogenesis by NO-related pathways.
动脉粥样硬化是一种与氧化型低密度脂蛋白（oxLDL）诱导的内皮细胞凋亡相关的血管壁慢性炎症性疾病。辅酶 Q10（CoQ10）是一种强效抗氧化剂，也是电子传递链的关键中间产物，已被报道可抑制 LDL 氧化，从而阻止动脉粥样硬化的进展。然而，其在内皮细胞上的分子机制仍不清楚。
本研究使用 oxLDL 处理的原代人脐静脉内皮细胞培养物来探讨 CoQ10 的保护作用。
我们的结果表明，CoQ10 可减轻 oxLDL 诱导的活性氧生成，并改善抗氧化能力。CoQ10 还可减轻 oxLDL 介导的内皮型一氧化氮合酶（eNOS）下调和诱导型一氧化氮合酶（iNOS）上调。此外，CoQ10 抑制 oxLDL 激活的 NF-κB 及下游炎症介质，包括黏附分子的表达、促炎细胞因子的释放和单核细胞 THP-1 细胞的黏附。此外，CoQ10 减轻 oxLDL 改变的促凋亡反应。使用 eNOS 抑制剂（L-NIO 10 μM）和 iNOS 抑制剂（1400W 10 μM）以及 NO 增强剂（SNP 10 μM）来清理相关机制。
这些结果为 CoQ10 通过 NO 相关途径保护动脉粥样硬化形成的可能分子机制提供了新的见解。
