α-lipoic acid prevents endothelial dysfunction in obese rats via activation of AMP-activated protein kinase

Woo Je Lee, Kyu Lee In, Sik Kim Hyoun, Mi Kim Yun, Hee Koh Eun, Chul Won Jong, Min Han Sung, Min Seon Kim, Inho Jo, Taeg Oh Goo, In Sun Park, Hyun Youn Jang, Seong Wook Park, Ki Up Lee, Joong Yeol Park

Research output: Contribution to journalArticlepeer-review

116 Scopus citations

Abstract

Objective - Lipid accumulation in vascular endothelial cells may play an important role in the pathogenesis of atherosclerosis in obese subjects. We showed previously that α-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. Methods and Results - 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. Conclusions - 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.

Original languageEnglish
Pages (from-to)2488-2494
Number of pages7
JournalArteriosclerosis, Thrombosis, and Vascular Biology
Volume25
Issue number12
DOIs
StatePublished - Dec 2005

Keywords

  • α-lipoic acid
  • AMPK
  • Endothelium
  • Oxidative stress
  • Vascular dysfunction

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