National Research Council-Institute of Clinical Physiology, Lecce, Italy.
Department of Basic Medical Sciences, Neurosciences and Sense Organs, University of Bari "Aldo Moro", Bari, Italy.
Oxid Med Cell Longev. 2018 Apr 18;2018:9086947. doi: 10.1155/2018/9086947. eCollection 2018.
Mitochondria are fundamental organelles producing energy and reactive oxygen species (ROS); their impaired functions play a key role in endothelial dysfunction. Hydroxytyrosol (HT), a well-known olive oil antioxidant, exerts health benefits against vascular diseases by improving endothelial function. However, the HT role in mitochondrial oxidative stress in endothelial dysfunction is not clear yet. To investigate the HT effects on mitochondrial ROS production in the inflamed endothelium, we used an model of endothelial dysfunction represented by cultured endothelial cells, challenged with phorbol myristate acetate (PMA), an inflammatory, prooxidant, and proangiogenic agent. We found that the pretreatment of endothelial cells with HT (1-30 mol/L) suppressed inflammatory angiogenesis, a crucial aspect of endothelial dysfunction. The HT inhibitory effect is related to reduced mitochondrial superoxide production and lipid peroxidation and to increased superoxide dismutase activity. HT, in a concentration-dependent manner, improved endothelial mitochondrial function by reverting the PMA-induced reduction of mitochondrial membrane potential, ATP synthesis, and ATP5 expression. In PMA-challenged endothelial cells, HT also promoted mitochondrial biogenesis through increased mitochondrial DNA content and expression of peroxisome proliferator-activated receptor gamma coactivator 1-alpha, nuclear respiratory factor-1, and mitochondrial transcription factor A. These results highlight that HT blunts endothelial dysfunction and pathological angiogenesis by ameliorating mitochondrial function, thus suggesting HT as a potential mitochondria-targeting antioxidant in the inflamed endothelium.
线粒体是产生能量和活性氧（ROS）的基本细胞器；其功能受损在血管内皮功能障碍中起着关键作用。羟基酪醇（HT）是一种众所周知的橄榄油抗氧化剂，通过改善内皮功能对血管疾病有健康益处。然而，HT 对内皮功能障碍中线粒体氧化应激的作用尚不清楚。为了研究 HT 对炎症内皮细胞中线粒体 ROS 产生的影响，我们使用了一种由佛波醇肉豆蔻酸酯（PMA）刺激的内皮细胞模型，PMA 是一种炎症、促氧化和促血管生成的试剂。我们发现，HT（1-30μmol/L）预处理内皮细胞可抑制炎症性血管生成，这是内皮功能障碍的一个重要方面。HT 的抑制作用与减少线粒体超氧化物产生和脂质过氧化以及增加超氧化物歧化酶活性有关。HT 以浓度依赖性方式通过逆转 PMA 诱导的线粒体膜电位、ATP 合成和 ATP5 表达降低来改善内皮细胞的线粒体功能。在 PMA 刺激的内皮细胞中，HT 还通过增加线粒体 DNA 含量和过氧化物酶体增殖物激活受体γ共激活因子 1-α、核呼吸因子-1 和线粒体转录因子 A 的表达来促进线粒体生物发生。这些结果强调了 HT 通过改善线粒体功能来减轻内皮功能障碍和病理性血管生成，因此提示 HT 作为一种潜在的线粒体靶向抗氧化剂在炎症内皮细胞中具有应用前景。
