Lee Woo Je, Lee In Kyu, Kim Hyoun Sik, Kim Yun Mi, Koh Eun Hee, Won Jong Chul, Han Sung Min, Kim Min-Seon, Jo Inho, Oh Goo Taeg, Park In-Sun, Youn Jang Hyun, Park Seong-Wook, Lee Ki-Up, Park Joong-Yeol
Department of Internal Medicine, University of Ulsan College of Medicine, Seoul, Republic of Korea.
Arterioscler Thromb Vasc Biol. 2005 Dec;25(12):2488-94. doi: 10.1161/01.ATV.0000190667.33224.4c. Epub 2005 Oct 13.
Lipid accumulation in vascular endothelial cells may play an important role in the pathogenesis of atherosclerosis in obese subjects. We showed previously that alpha-lipoic acid (ALA) activates AMP-activated protein kinase (AMPK) and reduces lipid accumulation in skeletal muscle of obese rats. Here, we investigated whether ALA improves endothelial dysfunction in obese rats by activating AMPK in endothelial cells.
Endothelium-dependent vascular relaxation was impaired, and the number of apoptotic endothelial cells was higher in the aorta of obese rats compared with control rats. In addition, triglyceride and lipid peroxide levels were higher, and NO synthesis was lower. Administration of ALA improved all of these abnormalities. AMPK activity was lower in aortic endothelium of obese rats, and ALA normalized it. Incubation of human aortic endothelial cells with ALA activated AMPK and protected cells from linoleic acid-induced apoptosis. Dominant-negative AMPK inhibited the antiapoptotic effects of ALA.
Reduced AMPK activation may play an important role in the genesis of endothelial dysfunction in obese rats. ALA improves vascular dysfunction by normalizing lipid metabolism and activating AMPK in endothelial cells.
血管内皮细胞中的脂质蓄积可能在肥胖个体动脉粥样硬化的发病机制中起重要作用。我们之前表明，α-硫辛酸（ALA）可激活AMP活化蛋白激酶（AMPK）并减少肥胖大鼠骨骼肌中的脂质蓄积。在此，我们研究了ALA是否通过激活内皮细胞中的AMPK来改善肥胖大鼠的内皮功能障碍。
与对照大鼠相比，肥胖大鼠主动脉的内皮依赖性血管舒张功能受损，凋亡内皮细胞数量更多。此外，甘油三酯和脂质过氧化物水平更高，一氧化氮合成更低。给予ALA改善了所有这些异常情况。肥胖大鼠主动脉内皮中的AMPK活性较低，而ALA使其恢复正常。用ALA孵育人主动脉内皮细胞可激活AMPK并保护细胞免受亚油酸诱导的凋亡。显性负性AMPK抑制了ALA的抗凋亡作用。
AMPK激活降低可能在肥胖大鼠内皮功能障碍的发生中起重要作用。ALA通过使脂质代谢正常化并激活内皮细胞中的AMPK来改善血管功能障碍。
