PMID- 15016641
OWN - NLM
STAT- MEDLINE
DCOM- 20041014
LR  - 20171116
IS  - 1524-4636 (Electronic)
IS  - 1079-5642 (Linking)
VI  - 24
IP  - 5
DP  - 2004 May
TI  - Overexpression of uncoupling protein 2 in THP1 monocytes inhibits beta2 
      integrin-mediated firm adhesion and transendothelial migration.
PG  - 864-70
AB  - 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 beta2 integrins, most notably 
      CD11b. UCP2 overexpression reduced beta2 integrin-mediated firm adhesion of 
      monocytes to either tumor necrosis factor-alpha (TNF-alpha)-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-alpha 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.
FAU - Ryu, Je-Won
AU  - Ryu JW
AD  - Department of Internal Medicine, Asan Medical Center, University of Ulsan College 
      of Medicine, Seoul, Republic of Korea.
FAU - Hong, Kyung Hee
AU  - Hong KH
FAU - Maeng, Jin Hee
AU  - Maeng JH
FAU - Kim, Jae-Bum
AU  - Kim JB
FAU - Ko, Jesang
AU  - Ko J
FAU - Park, Joong Yeol
AU  - Park JY
FAU - Lee, Ki-Up
AU  - Lee KU
FAU - Hong, Myeong Ki
AU  - Hong MK
FAU - Park, Seong Wook
AU  - Park SW
FAU - Kim, You Ho
AU  - Kim YH
FAU - Han, Ki Hoon
AU  - Han KH
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20040311
PL  - United States
TA  - Arterioscler Thromb Vasc Biol
JT  - Arteriosclerosis, thrombosis, and vascular biology
JID - 9505803
RN  - 0 (Actins)
RN  - 0 (Biopolymers)
RN  - 0 (CCR2 protein, human)
RN  - 0 (CD18 Antigens)
RN  - 0 (Cell Adhesion Molecules)
RN  - 0 (Chemokine CCL2)
RN  - 0 (Ion Channels)
RN  - 0 (Membrane Transport Proteins)
RN  - 0 (Mitochondrial Proteins)
RN  - 0 (RNA, Messenger)
RN  - 0 (Receptors, CCR2)
RN  - 0 (Receptors, Chemokine)
RN  - 0 (Recombinant Fusion Proteins)
RN  - 0 (Tumor Necrosis Factor-alpha)
RN  - 0 (UCP2 protein, human)
RN  - 0 (Ucp2 protein, mouse)
RN  - 0 (Uncoupling Protein 2)
SB  - IM
MH  - Actins/metabolism
MH  - Aorta/cytology
MH  - Arteriosclerosis/metabolism
MH  - Biopolymers
MH  - CD18 Antigens/biosynthesis/genetics/*physiology
MH  - Calcium Signaling
MH  - Cell Adhesion
MH  - Cell Adhesion Molecules/physiology
MH  - Cell Line/cytology/drug effects/metabolism
MH  - Cell Movement/drug effects
MH  - Chemokine CCL2/pharmacology
MH  - Endothelial Cells/cytology
MH  - Endothelium, Vascular/cytology
MH  - Gene Expression
MH  - Humans
MH  - Ion Channels
MH  - Membrane Transport Proteins/biosynthesis/genetics/*physiology
MH  - Microscopy, Confocal
MH  - Mitochondria/metabolism
MH  - Mitochondrial Proteins/biosynthesis/genetics/*physiology
MH  - Monocytes/cytology/drug effects/*metabolism
MH  - RNA, Messenger/biosynthesis
MH  - Receptors, CCR2
MH  - Receptors, Chemokine/physiology
MH  - Recombinant Fusion Proteins/biosynthesis/physiology
MH  - Transfection
MH  - Tumor Necrosis Factor-alpha/pharmacology
MH  - Uncoupling Protein 2
EDAT- 2004/03/16 05:00
MHDA- 2004/10/16 09:00
CRDT- 2004/03/16 05:00
PHST- 2004/03/16 05:00 [pubmed]
PHST- 2004/10/16 09:00 [medline]
PHST- 2004/03/16 05:00 [entrez]
AID - 01.ATV.0000125705.28058.eb [pii]
AID - 10.1161/01.ATV.0000125705.28058.eb [doi]
PST - ppublish
SO  - Arterioscler Thromb Vasc Biol. 2004 May;24(5):864-70. doi: 
      10.1161/01.ATV.0000125705.28058.eb. Epub 2004 Mar 11.