PMID- 15381392
OWN - NLM
STAT- MEDLINE
DCOM- 20050505
LR  - 20181130
IS  - 0049-3848 (Print)
IS  - 0049-3848 (Linking)
VI  - 114
IP  - 4
DP  - 2004
TI  - Reduced beta3-endonexin levels are associated with enhanced urokinase-type 
      plasminogen activator receptor expression in ApoE-/- mice.
PG  - 283-92
AB  - Proteolysis of extracellular matrix components is required for cell migration 
      occurring in atherosclerotic lesion formation. In the present study, gene 
      expression of the urokinase plasmingen activator receptor (uPAR) and underlying 
      mechanisms were analyzed during the development of atherosclerosis in the aorta 
      of apolipoprotein E-deficient mice (apoE(-/-)). A significant increase of uPAR 
      expression was detected in the atherosclerotic tissue with advancing 
      plaque-dimension. As uPAR gene transcription involves the transcription factor 
      nuclear factor-kappaB (NF-kappaB), we analyzed nuclear NF-kappaB activity in 
      vascular tissue of apoE-deficient mice. Congruent to uPAR, we could detect an 
      increase in NF-kappaB activity, which underlines the chronic inflammatory 
      component of the disease. Recently we reported that beta(3)-endonexin, a protein 
      that modulates beta(3)-integrins, regulates uPAR expression through direct 
      interaction with subunits of the NF-kappaB-complex. Herein we could show that 
      beta(3)-endonexin protein is expressed in aortic tissue of mice. Moreover, in 
      contrast to uPAR or NF-kappaB, the expression of beta(3)-endonexin was reduced in 
      extracts of advanced atherosclerotic aortic tissue. The cytoplasmic protein 
      beta(3)-endonexin regulates function of beta(3)-integrins. We revealed that 
      integrin stimulation of endothelial cells led to an enhanced NF-kappaB activity 
      and secretion of the NF-kappaB dependent chemokine monocyte chemoattractant 
      protein-1 (MCP-1). The beta(3)-integrin dependent increase in MCP-1 was notedly 
      reduced in cells that overexpressed beta(3)-endonexin. These results provide 
      strong evidence that beta(3)-endonexin acts as a regulating factor in the 
      integrin-mediated signal transduction and the present findings imply a 
      pathophysiological role of beta(3)-endonexin in atherogenesis.
FAU - Besta, F
AU  - Besta F
AD  - Deutsches Herzzentrum Munchen, Lazarettstrasse 36, 80636 Munich, Germany.
FAU - Muller, I
AU  - Muller I
FAU - Lorenz, M
AU  - Lorenz M
FAU - Massberg, S
AU  - Massberg S
FAU - Bultmann, A
AU  - Bultmann A
FAU - Cabeza, N
AU  - Cabeza N
FAU - Richter, T
AU  - Richter T
FAU - Kremmer, E
AU  - Kremmer E
FAU - Nothdurfter, C
AU  - Nothdurfter C
FAU - Brand, K
AU  - Brand K
FAU - Gawaz, M
AU  - Gawaz M
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Thromb Res
JT  - Thrombosis research
JID - 0326377
RN  - 0 (Apolipoproteins E)
RN  - 0 (Ccl2 protein, mouse)
RN  - 0 (Chemokine CCL2)
RN  - 0 (ITGB3BP protein, human)
RN  - 0 (Integrin beta3)
RN  - 0 (NF-kappa B)
RN  - 0 (Nuclear Proteins)
RN  - 0 (PLAUR protein, human)
RN  - 0 (Plaur protein, mouse)
RN  - 0 (Proteins)
RN  - 0 (Receptors, Cell Surface)
RN  - 0 (Receptors, Urokinase Plasminogen Activator)
SB  - IM
MH  - Animals
MH  - Aortic Diseases/etiology
MH  - Apolipoproteins E/deficiency/genetics
MH  - Arteriosclerosis/*etiology
MH  - Chemokine CCL2/metabolism
MH  - Disease Models, Animal
MH  - Endothelium, Vascular/metabolism/pathology
MH  - *Gene Expression Regulation
MH  - Humans
MH  - Integrin beta3/pharmacology
MH  - Mice
MH  - NF-kappa B/metabolism
MH  - Nuclear Proteins
MH  - Proteins/analysis/*physiology
MH  - Receptors, Cell Surface/*genetics
MH  - Receptors, Urokinase Plasminogen Activator
MH  - Umbilical Veins/cytology
EDAT- 2004/09/24 05:00
MHDA- 2005/05/06 09:00
CRDT- 2004/09/24 05:00
PHST- 2003/10/19 00:00 [received]
PHST- 2004/02/19 00:00 [revised]
PHST- 2004/02/23 00:00 [accepted]
PHST- 2004/09/24 05:00 [pubmed]
PHST- 2005/05/06 09:00 [medline]
PHST- 2004/09/24 05:00 [entrez]
AID - S0049384804001136 [pii]
AID - 10.1016/j.thromres.2004.02.021 [doi]
PST - ppublish
SO  - Thromb Res. 2004;114(4):283-92. doi: 10.1016/j.thromres.2004.02.021.