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(Circulation Research. 2005;96:1200.)
© 2005 American Heart Association, Inc.

Integrative Physiology

Effects of Recombinant Adenovirus-Mediated Uncoupling Protein 2 Overexpression on Endothelial Function and Apoptosis

Ki-Up Lee^*, In Kyu Lee^*, Jin Han, Dae-Kyu Song, Yun Mi Kim, Hai Sun Song, Hyoun Sik Kim, Woo Je Lee, Eun Hee Koh, Kee-Ho Song, Sung Min Han, Min Seon Kim, In-Sun Park, Joong-Yeol Park

From the University of Ulsan College of Medicine (K.-U.L., W.J.L., E.H.K., K.-H.S., S.M.H., M.S.K., J.-Y.P.), Seoul, Korea; School of Medicine (I.K.L.), Kyungpook National University, Daegu, Korea; College of Medicine (D.-K.S.), Keimyung University, Daegu, Korea; College of Medicine (J.H.), Inje University, Pusan, Korea; Asan Institute for Life Sciences (Y.M.K., H.S.S., H.S.K.), Seoul, Korea; Inha University College of Medicine (I.S.P.), Inchon, Korea.

Correspondence to Dr Joong-Yeol Park, Department of Internal Medicine, University of Ulsan College of Medicine, Asan Medical Center, Song-Pa P.O. Box 145, Seoul 138-600, Korea. E-mail jypark{at}amc.seoul.kr

Increased oxidative stress in vascular cells plays a key role in the development of endothelial dysfunction and atherosclerosis. Uncoupling protein 2 (UCP2) is an important regulator of intracellular reactive oxygen species (ROS) production. This study was undertaken to test the hypothesis that, UCP2 functions as an inhibitor of the atherosclerotic process in endothelial cells. Adenovirus-mediated UCP2 (Ad-UCP2) overexpression led to a significant increase in endothelial nitric oxide synthase (eNOS) and decrease in endothelin-1 mRNA expression in human aortic endothelial cells (HAECs). Moreover, UCP2 inhibited the increase in ROS production and NF-B activation, and apoptosis of HAECs induced by lysophophatidylcholine (LPC) and linoleic acid. LPC and linoleic acid caused mitochondrial calcium accumulation and transient mitochondrial membrane hyperpolarization, which was followed by depolarization. UCP2 overexpression prevented these processes. In isolated rat aorta, Ad-UCP2 infection markedly improved impaired vascular relaxation induced by LPC. The data collectively suggest that UCP2, functions as a physiologic regulator of ROS generation in endothelial cells. Thus, measures to increase UCP2 expression in vascular endothelial cells may aid in preventing the development and progression of atherosclerosis in patients with metabolic syndrome.

Key Words: endothelial cells • uncoupling protein • oxidative stress • vascular endothelial function • apoptosis

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