Published online before print October 13, 2005, doi: 10.1161/01.ATV.0000190667.33224.4c
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© 2005 American Heart Association, Inc.
Vascular Biology |
-Lipoic Acid Prevents Endothelial Dysfunction in Obese Rats via Activation of AMP-Activated Protein Kinase
From the Department of Internal Medicine (W.J.L, E.H.K., J.C.W., S.M.H., M.-S.K., S.W.P., K.-U.L., J.-Y.P.), Asan Institute for Life Sciences (H.S.K., Y.M.K.), University of Ulsan College of Medicine, Seoul, Republic of Korea; the Department of Internal Medicine (I.K.L.), Kyungpook National University School of Medicine, Daegu, Republic of Korea; the Division of Cardiovascular Research (I.J.), Korean National Institute of Health, Seoul, Republic of Korea; the Laboratory of Cardiovascular Genomics (G.T.O.), Division of Molecular Life Sciences, Ewha Woman’s University, Seoul, Republic of Korea; the Department of Anatomy (I.-S.P.), Inha University College of Medicine, Incheon, Republic of Korea; and the Department of Physiology and Biophysics (J.H.Y.), University of Southern California Keck School of Medicine, Los Angeles.
Correspondence to Joong-Yeol Park, Department of Internal Medicine, University of Ulsan College of Medicine, Asan Medical Center, Song-Pa PO Box 145, Seoul 138-600, Republic of Korea. E-mail jypark{at}amc.seoul.kr
Objective— Lipid accumulation in vascular endothelial cells may play an important role in the pathogenesis of atherosclerosis in obese subjects. We showed previously that 
-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.
We tested whether reduced AMP-activated protein kinase (AMPK) activity in vascular endothelial cells is responsible for endothelial dysfunction in obese rats. -Lipoic acid (ALA) improved endothelial dysfunction and normalized AMPK activity in obese rats. This study provides a rationale for the therapeutic use of ALA for vascular dysfunction.
Key Words: -lipoic acid • endothelium • AMPK • oxidative stress • vascular dysfunction
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