PMID- 14699006
OWN - NLM
STAT- MEDLINE
DCOM- 20040209
LR  - 20220331
IS  - 1524-4539 (Electronic)
IS  - 0009-7322 (Linking)
VI  - 109
IP  - 3
DP  - 2004 Jan 27
TI  - Toll-like receptor 4 is involved in outward arterial remodeling.
PG  - 393-8
AB  - BACKGROUND: Toll-like receptor 4 (Tlr4) is the receptor for exogenous 
      lipopolysaccharides (LPS). Expression of endogenous Tlr4 ligands, heat shock 
      protein 60 (Hsp60) and extra domain A of fibronectin, has been observed in 
      arthritic and oncological specimens in which matrix turnover is an important 
      feature. In atherosclerosis, outward remodeling is characterized by matrix 
      turnover and a structural change in arterial circumference and is associated with 
      a vulnerable plaque phenotype. Since Tlr4 ligands are expressed during matrix 
      turnover, we hypothesized that Tlr4 is involved in arterial remodeling. METHODS 
      AND RESULTS: In a femoral artery cuff model in the atherosclerotic ApoE3 (Leiden) 
      transgenic mouse, Tlr4 activation by LPS stimulated plaque formation and 
      subsequent outward arterial remodeling. With the use of the same model in 
      wild-type mice, neointima formation and outward remodeling occurred. In 
      Tlr4-deficient mice, however, no outward arterial remodeling was observed 
      independent of neointima formation. Carotid artery ligation in wild-type mice 
      resulted in outward remodeling without neointima formation in the contralateral 
      artery. This was associated with an increase in Tlr4 expression and EDA and Hsp60 
      mRNA levels. In contrast, outward remodeling was not observed after carotid 
      ligation in Tlr4-deficient mice. CONCLUSIONS: These findings provide genetic 
      evidence that Tlr4 is involved in outward arterial remodeling, probably through 
      upregulation of Tlr4 and Tlr4 ligands.
FAU - Hollestelle, Saskia C G
AU  - Hollestelle SC
AD  - Experimental Cardiology Laboratory, University Medical Center, Room G02-523, 
      Heidelberglaan 100, 3584 CX Utrecht, The Netherlands. d.dekleijn@hli.azu.nl
FAU - De Vries, Margreet R
AU  - De Vries MR
FAU - Van Keulen, J Karlijn
AU  - Van Keulen JK
FAU - Schoneveld, Arjan H
AU  - Schoneveld AH
FAU - Vink, Aryan
AU  - Vink A
FAU - Strijder, Chaylendra F
AU  - Strijder CF
FAU - Van Middelaar, Ben J
AU  - Van Middelaar BJ
FAU - Pasterkamp, Gerard
AU  - Pasterkamp G
FAU - Quax, Paul H A
AU  - Quax PH
FAU - De Kleijn, Dominique P V
AU  - De Kleijn DP
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20031229
PL  - United States
TA  - Circulation
JT  - Circulation
JID - 0147763
RN  - 0 (Apolipoprotein E3)
RN  - 0 (Apolipoproteins E)
RN  - 0 (Ligands)
RN  - 0 (Membrane Glycoproteins)
RN  - 0 (Receptors, Cell Surface)
RN  - 0 (Toll-Like Receptor 4)
RN  - 0 (Toll-Like Receptors)
RN  - 0 (apolipoprotein E3 (Leidein))
SB  - IM
MH  - Animals
MH  - Apolipoprotein E3
MH  - Apolipoproteins E/genetics
MH  - Arteries/*pathology
MH  - Arteriosclerosis/etiology/*pathology
MH  - Carotid Arteries/pathology
MH  - Female
MH  - Femoral Artery/pathology
MH  - Ligands
MH  - Membrane Glycoproteins/genetics/*physiology
MH  - Mice
MH  - Mice, Knockout
MH  - Mice, Transgenic
MH  - Receptors, Cell Surface/genetics/*physiology
MH  - Toll-Like Receptor 4
MH  - Toll-Like Receptors
EDAT- 2003/12/31 05:00
MHDA- 2004/02/11 05:00
CRDT- 2003/12/31 05:00
PHST- 2003/12/31 05:00 [pubmed]
PHST- 2004/02/11 05:00 [medline]
PHST- 2003/12/31 05:00 [entrez]
AID - 01.CIR.0000109140.51366.72 [pii]
AID - 10.1161/01.CIR.0000109140.51366.72 [doi]
PST - ppublish
SO  - Circulation. 2004 Jan 27;109(3):393-8. doi: 10.1161/01.CIR.0000109140.51366.72. 
      Epub 2003 Dec 29.