PMID- 17053192
OWN - NLM
STAT- MEDLINE
DCOM- 20070306
LR  - 20220310
IS  - 1524-4571 (Electronic)
IS  - 0009-7330 (Linking)
VI  - 99
IP  - 11
DP  - 2006 Nov 24
TI  - Fcgamma receptor deficiency confers protection against atherosclerosis in 
      apolipoprotein E knockout mice.
PG  - 1188-96
AB  - IgG Fc receptors (FcgammaRs) play a role in activating the immune system and in 
      maintaining peripheral tolerance, but their role in atherosclerosis is unknown. 
      We generated double-knockout (DKO) mice by crossing apolipoprotein E-deficient 
      mice (apoE(-/-)) with FcgammaR gamma chain-deficient mice (gamma(-/-)). The size 
      of atherosclerotic lesions along the aorta was approximately 50% lower in DKO 
      compared with apoE(-/-) control mice, without differences in serum lipid levels. 
      The macrophage and T-cell content of lesions in the DKO were reduced by 49+/-6% 
      and 56+/-8%, respectively, compared with the content in apoE(-/-) lesions. 
      Furthermore, the expression of monocyte chemoattractant protein-1 (MCP-1), RANTES 
      (Regulated on Activated Normal T-cell Expressed and Secreted), and intercellular 
      adhesion molecule-1 (ICAM-1) and the activation of nuclear factor-kappaB 
      (NF-kappaB) were significantly reduced in aortic lesions from DKO mice. In vitro, 
      vascular smooth muscle cells (VSMCs) from both gamma(-/-) and DKO mice failed to 
      respond to immune complexes, as shown by impaired chemokine expression and 
      NF-kappaB activation. ApoE(-/-) mice have higher levels of activating FcgammaRI 
      and FcgammaRIIIA, and inhibitory FcgammaRIIB, compared with wild-type mice. The 
      DKO mice express only the inhibitory FcgammaRIIB receptor. We conclude that 
      FcgammaR deficiency limits development and progression of atherosclerosis. In 
      addition to leukocytes, FcgammaR activation in VSMCs contributes to the 
      inflammatory process, in part, by regulating chemokine expression and leukocyte 
      invasion of the vessel wall. These results underscore the critical role of 
      FcgammaRs in atherogenesis and support the use of immunotherapy in the treatment 
      of this disease.
FAU - Hernandez-Vargas, Purificacion
AU  - Hernandez-Vargas P
AD  - Renal and Vascular Research Laboratory, Fundacion Jimenez Diaz, Autonoma 
      University, Madrid, Spain.
FAU - Ortiz-Munoz, Guadalupe
AU  - Ortiz-Munoz G
FAU - Lopez-Franco, Oscar
AU  - Lopez-Franco O
FAU - Suzuki, Yusuke
AU  - Suzuki Y
FAU - Gallego-Delgado, Julio
AU  - Gallego-Delgado J
FAU - Sanjuan, Guillermo
AU  - Sanjuan G
FAU - Lazaro, Alberto
AU  - Lazaro A
FAU - Lopez-Parra, Virginia
AU  - Lopez-Parra V
FAU - Ortega, Luis
AU  - Ortega L
FAU - Egido, Jesus
AU  - Egido J
FAU - Gomez-Guerrero, Carmen
AU  - Gomez-Guerrero C
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20061019
PL  - United States
TA  - Circ Res
JT  - Circulation research
JID - 0047103
RN  - 0 (Antigen-Antibody Complex)
RN  - 0 (Apolipoproteins E)
RN  - 0 (Chemokines)
RN  - 0 (FcgammaRIIIA protein, mouse)
RN  - 0 (Fcgr1 protein, mouse)
RN  - 0 (Fcgr2b protein, mouse)
RN  - 0 (Inflammation Mediators)
RN  - 0 (NF-kappa B)
RN  - 0 (Receptors, IgG)
SB  - IM
CIN - Circ Res. 2006 Nov 24;99(11):1154-5. PMID: 17122444
MH  - Animals
MH  - Antigen-Antibody Complex/metabolism
MH  - Apolipoproteins E/*deficiency
MH  - Atherosclerosis/etiology/*prevention & control
MH  - Cells, Cultured
MH  - Chemokines/metabolism
MH  - Down-Regulation
MH  - Female
MH  - Gene Expression
MH  - Inflammation Mediators/metabolism
MH  - Male
MH  - Mice
MH  - Mice, Knockout
MH  - Muscle, Smooth, Vascular/cytology/metabolism
MH  - Myocytes, Smooth Muscle/metabolism
MH  - NF-kappa B/metabolism
MH  - Receptors, IgG/*deficiency/metabolism
EDAT- 2006/10/21 09:00
MHDA- 2007/03/07 09:00
CRDT- 2006/10/21 09:00
PHST- 2006/10/21 09:00 [pubmed]
PHST- 2007/03/07 09:00 [medline]
PHST- 2006/10/21 09:00 [entrez]
AID - 01.RES.0000250556.07796.6c [pii]
AID - 10.1161/01.RES.0000250556.07796.6c [doi]
PST - ppublish
SO  - Circ Res. 2006 Nov 24;99(11):1188-96. doi: 10.1161/01.RES.0000250556.07796.6c. 
      Epub 2006 Oct 19.