Effects of recombinant adenovirus-mediated uncoupling protein 2 overexpression on endothelial function and apoptosis.
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-kappaB 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.
Lee
Ki-Up
KU
University of Ulsan College of Medicine, Seoul, Korea.
Lee
In Kyu
IK
Han
Jin
J
Song
Dae-Kyu
DK
Kim
Yun Mi
YM
Song
Hai Sun
HS
Kim
Hyoun Sik
HS
Lee
Woo Je
WJ
Koh
Eun Hee
EH
Song
Kee-Ho
KH
Han
Sung Min
SM
Kim
Min Seon
MS
Park
In-Sun
IS
Park
Joong-Yeol
JY
D000256:Adenoviridae / Q000235:genetics*; D017209:Apoptosis; D001161:Arteriosclerosis / Q000517:prevention & control*; D002118:Calcium / Q000378:metabolism; D020169:Caspases / Q000378:metabolism; D002478:Cells, Cultured; D004579:Electron Transport; D042783:Endothelial Cells / Q000502:physiology*; D019332:Endothelin-1 / Q000235:genetics; D022761:Gene Transfer, Horizontal; D006801:Humans; D007473:Ion Channels; D019787:Linoleic Acid / Q000494:pharmacology; D008244:Lysophosphatidylcholines / Q000494:pharmacology; D026901:Membrane Transport Proteins / Q000235:genetics / Q000502:physiology*; D024101:Mitochondrial Proteins / Q000235:genetics / Q000502:physiology*; D016328:NF-kappa B / Q000378:metabolism; D009569:Nitric Oxide / Q000032:analysis; D019001:Nitric Oxide Synthase / Q000235:genetics; D052250:Nitric Oxide Synthase Type III; D012333:RNA, Messenger / Q000032:analysis; D017382:Reactive Oxygen Species; D000071246:Uncoupling Protein 2
D019332:Endothelin-1; D007473:Ion Channels; D008244:Lysophosphatidylcholines; D026901:Membrane Transport Proteins; D024101:Mitochondrial Proteins; D016328:NF-kappa B; D012333:RNA, Messenger; D017382:Reactive Oxygen Species; C000604389:UCP2 protein, human; C000604391:Ucp2 protein, rat; D000071246:Uncoupling Protein 2; D009569:Nitric Oxide; D019787:Linoleic Acid; C496314:NOS3 protein, human; D019001:Nitric Oxide Synthase; D052250:Nitric Oxide Synthase Type III; D020169:Caspases; D002118:Calcium