Adenovirus-mediated UCP2 overexpression increased eNOS, decreased endothelin-1, and inhibited ROS production and apoptosis in human aortic endothelial cells.
Does adenovirus-mediated UCP2 overexpression improve endothelial function and prevent apoptosis in human aortic endothelial cells and isolated rat aorta?
UCP2 overexpression protects against endothelial dysfunction and apoptosis by regulating ROS generation, suggesting a potential therapeutic target for atherosclerosis in metabolic syndrome.
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 et al. (2005) studied Endothelial dysfunction and atherosclerosis. Adenovirus-mediated UCP2 (Ad-UCP2) overexpression was evaluated on Endothelial function, ROS production, and apoptosis. Adenovirus-mediated UCP2 overexpression increased eNOS, decreased endothelin-1, and inhibited ROS production and apoptosis in human aortic endothelial cells.