Effects of recombinant adenovirus-mediated uncoupling protein 2 overexpression on endothelial function and apoptosis
Effects of recombinant adenovirus-mediated uncoupling protein 2 overexpression on endothelial function and apoptosis
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DOI：
10.1161/01.res.0000170075.73039.5b
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发表时间：
2005-06-10
影响因子：
20.1
通讯作者：
Park, JY
中科院分区：
文献类型：
--
作者：
Lee, KU;Lee, IK;Park, JY
血管细胞中氧化应激的增加在内皮功能障碍和动脉粥样硬化的发展中起关键作用。解偶联蛋白2（UCP 2）是细胞内活性氧（ROS）产生的重要调节因子。本研究旨在验证UCP 2在内皮细胞中作为动脉粥样硬化过程抑制剂的假设。腺病毒介导的UCP 2（Ad-UCP 2）过表达导致人主动脉内皮细胞（HAECs）内皮型一氧化氮合酶（eNOS）表达显著增加，内皮素-1（ET-1）mRNA表达显著降低。UCP 2还能抑制LPC和亚油酸诱导的HAECs的ROS生成和NF-κ B活化，以及凋亡。LPC和亚油酸引起线粒体钙积累和短暂的线粒体膜超极化，然后去极化。UCP 2过度表达阻止了这些过程。在离体大鼠主动脉，Ad-UCP 2感染显着改善LPC诱导的血管舒张受损。这些数据共同表明，UCP 2作为内皮细胞中ROS产生的生理调节剂发挥作用。因此，增加血管内皮细胞中UCP 2表达的措施可能有助于预防代谢综合征患者动脉粥样硬化的发展和进展。
Increased oxidative stress in vascular cells plays a key role in the development of endothelial dysfunction and atherosclerosis. Uncoupling protein 2 (UCP2) is an important regulator of intracellular reactive oxygen species (ROS) production. This study was undertaken to test the hypothesis that, UCP2 functions as an inhibitor of the atherosclerotic process in endothelial cells. Adenovirus-mediated UCP2 (Ad-UCP2) overexpression led to a significant increase in endothelial nitric oxide synthase ( eNOS) and decrease in endothelin-1 mRNA expression in human aortic endothelial cells (HAECs). Moreover, UCP2 inhibited the increase in ROS production and NF-kappa B activation, and apoptosis of HAECs induced by lysophophatidylcholine (LPC) and linoleic acid. LPC and linoleic acid caused mitochondrial calcium accumulation and transient mitochondrial membrane hyperpolarization, which was followed by depolarization. UCP2 overexpression prevented these processes. In isolated rat aorta, Ad-UCP2 infection markedly improved impaired vascular relaxation induced by LPC. The data collectively suggest that UCP2, functions as a physiologic regulator of ROS generation in endothelial cells. Thus, measures to increase UCP2 expression in vascular endothelial cells may aid in preventing the development and progression of atherosclerosis in patients with metabolic syndrome.