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(Arteriosclerosis, Thrombosis, and Vascular Biology. 2004;24:864.)
© 2004 American Heart Association, Inc.

Vascular Biology

Overexpression of Uncoupling Protein 2 in THP1 Monocytes Inhibits ß₂ Integrin-Mediated Firm Adhesion and Transendothelial Migration

Je-Won Ryu; Kyung Hee Hong; Jin Hee Maeng; Jae-Bum Kim; Jesang Ko; Joong Yeol Park; Ki-Up Lee; Myeong Ki Hong; Seong Wook Park; You Ho Kim; Ki Hoon Han

From the Department of Internal Medicine (J-W.R., K.H.H., J.H.M., J.K., J.Y.P., K.-U.L., M.K.H., S.W.P., Y.H.K., K.H.H), Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea; and the School of Biological Sciences (J.-W.R., J.-B.K.), Seoul National University, Seoul, Republic of Korea.

Correspondence to Ki Hoon Han, Asan Medical Center 388-1 Pungnap-2 dong Songpa-gu 138-736 Seoul, South Korea. E-mail steadyhan{at}amc.seoul.kr

Objective— Uncoupling protein 2 (UCP2) belongs to the mitochondrial anion carrier family and regulates production of reactive oxygen species in macrophages. Previous studies have shown that selective genetic disruption of UCP2 in bone marrow cells results in excess accumulation of monocytes/macrophages in the vascular wall of hypercholesterolemic low-density lipoprotein receptor-deficient (LDLR^–/–) mice. Here we investigated whether UCP2 regulates expression of genes involved in monocyte recruitment.

Methods and Results— UCP2 overexpression in THP1 monocytes, which induced a 10-fold increase in mitochondrial UCP2 protein levels, reduced steady-state level of intracellular reactive oxygen species (ROS) and H₂O₂-induced ROS production. THP1 monocytes with UCP2 overexpression showed lower intracellular calcium levels and less H₂O₂-triggered intracellular calcium mobilization, and less protein and mRNA levels of ß₂ integrins, most notably CD11b. UCP2 overexpression reduced ß₂ integrin-mediated firm adhesion of monocytes to either tumor necrosis factor- (TNF-)–stimulated human aortic endothelial cell (HAEC) monolayers or to plates coated with intercellular adhesion molecule-1, not vascular cell adhesion molecule-1. UCP2 overexpression also inhibited cell spreading and actin polymerization in monocytes treated with TNF- and monocyte chemoattractant protein-1 (MCP-1), and reduced MCP-1–induced transmigration of monocytes through HAEC monolayers.

Conclusions— Mitochondrial UCP2 in circulating monocytes may prevent excessive accumulation of monocytes/macrophages in the arterial wall, thereby reducing atherosclerotic plaque formation.

Key Words: UCP2 • monocytes • integrins • adhesion • atherosclerosis

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