α-Lipoic Acid Prevents Endothelial Dysfunction in Obese Rats via Activation of AMP-Activated Protein Kinase

• Published in: Arteriosclerosis, thrombosis, and vascular biology Vol. 25; no. 12; pp. 2488 - 2494
• Main Authors: 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
• Format: Journal Article
• Language: English
• Published: Philadelphia, PA American Heart Association, Inc 01.12.2005; Hagerstown, MD Lippincott
• Subjects: Adenoviridae - genetics; Animals; Aorta - metabolism; Aorta - pathology; Aorta - physiopathology; Apoptosis - drug effects; Apoptosis - physiology; Associated diseases and complications; Atherosclerosis (general aspects, experimental research); Atherosclerosis - metabolism; Atherosclerosis - pathology; Atherosclerosis - physiopathology; Biological and medical sciences; Blood and lymphatic vessels; Cardiology. Vascular system; Cells, Cultured; Diabetes. Impaired glucose tolerance; Diseases of the peripheral vessels. Diseases of the vena cava. Miscellaneous; Endocrine pancreas. Apud cells (diseases); Endocrinopathies; Endothelium, Vascular - drug effects; Endothelium, Vascular - metabolism; Endothelium, Vascular - pathology; Gene Transfer Techniques; Genes, Dominant; Humans; Male; Medical sciences; Membrane Potentials - drug effects; Membrane Potentials - physiology; Mitochondria - physiology; NADPH Oxidases - metabolism; Nitric Oxide Synthase - metabolism; Non tumoral diseases. Target tissue resistance. Benign neoplasms; Obesity - metabolism; Obesity - pathology; Obesity - physiopathology; Phosphorylation; Protein Kinases - genetics; Protein Kinases - metabolism; Rats; Rats, Inbred OLETF; Thioctic Acid - metabolism; Thioctic Acid - pharmacology; Thyroid. Thyroid axis (diseases); Triglycerides - metabolism; Vasodilation - drug effects; Vasodilation - physiology; Obesity; Oxidative stress; AMP; Rat; Enzyme; Transferases; Rodentia; Nutrition disorder; Cardiovascular disease; α-lipoic acid; Endothelium; Vascular disease; Vertebrata; Mammalia; vascular dysfunction; Protein kinase; Animal; Atherosclerosis; Endothelial dysfunction; AMPK; Nutritional status
• ISSN: 1079-5642; 1524-4636
• DOI: 10.1161/01.ATV.0000190667.33224.4c

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.