title: Alpha-lipoic acid prevents endothelial dysfunction in obese rats via activation of AMP-activated protein kinase.
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 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.
  
  
  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.
authors.affiliation: Department of Internal Medicine, University of Ulsan College of Medicine, Seoul, Republic of Korea.
authors.forename: Woo Je
authors.initials: WJ
authors.lastname: Lee
authors.forename: In Kyu
authors.initials: IK
authors.lastname: Lee
authors.forename: Hyoun Sik
authors.initials: HS
authors.lastname: Kim
authors.forename: Yun Mi
authors.initials: YM
authors.lastname: Kim
authors.forename: Eun Hee
authors.initials: EH
authors.lastname: Koh
authors.forename: Jong Chul
authors.initials: JC
authors.lastname: Won
authors.forename: Sung Min
authors.initials: SM
authors.lastname: Han
authors.forename: Min-Seon
authors.initials: MS
authors.lastname: Kim
authors.forename: Inho
authors.initials: I
authors.lastname: Jo
authors.forename: Goo Taeg
authors.initials: GT
authors.lastname: Oh
authors.forename: In-Sun
authors.initials: IS
authors.lastname: Park
authors.forename: Jang Hyun
authors.initials: JH
authors.lastname: Youn
authors.forename: Seong-Wook
authors.initials: SW
authors.lastname: Park
authors.forename: Ki-Up
authors.initials: KU
authors.lastname: Lee
authors.forename: Joong-Yeol
authors.initials: JY
authors.lastname: Park
mesh_terms: D000091162:AMP-Activated Protein Kinase Kinases; D000256:Adenoviridae / Q000235:genetics; D000818:Animals; D001011:Aorta / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D017209:Apoptosis / Q000187:drug effects / Q000502:physiology; D050197:Atherosclerosis / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D002478:Cells, Cultured; D004730:Endothelium, Vascular / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D018014:Gene Transfer Techniques; D005799:Genes, Dominant; D006801:Humans; D008297:Male; D008564:Membrane Potentials / Q000187:drug effects / Q000502:physiology; D008928:Mitochondria / Q000502:physiology; D019255:NADPH Oxidases / Q000378:metabolism; D019001:Nitric Oxide Synthase / Q000378:metabolism; D009765:Obesity / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D010766:Phosphorylation; D011494:Protein Kinases / Q000235:genetics / Q000378:metabolism*; D051381:Rats; D020334:Rats, Inbred OLETF; D008063:Thioctic Acid / Q000378:metabolism* / Q000494:pharmacology; D014280:Triglycerides / Q000378:metabolism; D014664:Vasodilation / Q000187:drug effects / Q000502:physiology
chemical_list: D014280:Triglycerides; D008063:Thioctic Acid; D019001:Nitric Oxide Synthase; D019255:NADPH Oxidases; D011494:Protein Kinases; D000091162:AMP-Activated Protein Kinase Kinases