PMID- 18456733
OWN - NLM
STAT- MEDLINE
DCOM- 20080815
LR  - 20200930
IS  - 0363-6135 (Print)
IS  - 0363-6135 (Linking)
VI  - 294
IP  - 6
DP  - 2008 Jun
TI  - Wnt5a is expressed in murine and human atherosclerotic lesions.
PG  - H2864-70
LID - 10.1152/ajpheart.00982.2007 [doi]
AB  - Atherosclerosis is an inflammatory disease involving the accumulation of 
      macrophages in the intima. Wnt5a is a noncanonical member of the Wnt family of 
      secreted glycoproteins. Recently, human macrophages have been shown to express 
      Wnt5a upon stimulation with bacterial pathogens in vitro and in granulomatous 
      lesions in the lung of Mycobacterium tuberculosis-infected patients. Wnt5a 
      expression has also been liked to Toll-like receptor-4 (TLR-4), an innate immune 
      receptor implicated in atherosclerosis. These observations, along with the fact 
      that Wnt5a is involved in cell migration and proliferation, led us to postulate 
      that Wnt5a plays a role in atherosclerosis. To investigate this hypothesis, we 
      characterized Wnt5a expression in murine and human atherosclerotic lesions. 
      Tissue sections derived from the aortic sinus to the aortic arch of 
      apolipoprotein E-deficient mice and sections derived from the carotid arteries of 
      patients undergoing endarterectomy were subjected to immunohistochemical 
      analysis. All samples were found to be positive for Wnt5a with predominant 
      staining in the areas of macrophage accumulation within the intima. In parallel, 
      we probed for the presence of TLR-4 and found coincident TLR-4 and Wnt5a 
      expression. For both the Wnt5a and TLR-4 staining, consecutive tissue sections 
      treated with an isotype- and species-matched Ig served as a negative control and 
      exhibited little, if any, reactivity. Quantitative RT-PCR revealed that Wnt5a 
      mRNA expression in RAW264.7 murine macrophages can be induced by stimulation with 
      LPS, a known ligand for TLR-4. Combined, these findings demonstrate for the first 
      time Wnt5a expression in human and murine atherosclerotic lesions and suggest 
      that cross talk between TLR-4 and Wnt5a is operative in atherosclerosis.
FAU - Christman, Mark A 2nd
AU  - Christman MA 2nd
AD  - Department of Chemical and Biomolecular Engineering, Ohio University, Columbus, 
      Ohio, USA.
FAU - Goetz, Douglas J
AU  - Goetz DJ
FAU - Dickerson, Eric
AU  - Dickerson E
FAU - McCall, Kelly D
AU  - McCall KD
FAU - Lewis, Christopher J
AU  - Lewis CJ
FAU - Benencia, Fabian
AU  - Benencia F
FAU - Silver, Mitchell J
AU  - Silver MJ
FAU - Kohn, Leonard D
AU  - Kohn LD
FAU - Malgor, Ramiro
AU  - Malgor R
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20080502
PL  - United States
TA  - Am J Physiol Heart Circ Physiol
JT  - American journal of physiology. Heart and circulatory physiology
JID - 100901228
RN  - 0 (Apolipoproteins E)
RN  - 0 (Lipopolysaccharides)
RN  - 0 (Proto-Oncogene Proteins)
RN  - 0 (RNA, Messenger)
RN  - 0 (TLR4 protein, human)
RN  - 0 (Tlr4 protein, mouse)
RN  - 0 (Toll-Like Receptor 4)
RN  - 0 (WNT5A protein, human)
RN  - 0 (Wnt Proteins)
RN  - 0 (Wnt-5a Protein)
RN  - 0 (Wnt5a protein, mouse)
SB  - IM
MH  - Animals
MH  - Aortic Diseases/*metabolism/pathology
MH  - Apolipoproteins E/genetics/metabolism
MH  - Atherosclerosis/*metabolism/pathology
MH  - Carotid Artery Diseases/*metabolism/pathology
MH  - Cell Line
MH  - Disease Models, Animal
MH  - Female
MH  - Humans
MH  - Immunohistochemistry
MH  - Lipopolysaccharides/pharmacology
MH  - Macrophages/*chemistry/drug effects/metabolism
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Mice, Knockout
MH  - Proto-Oncogene Proteins/*analysis
MH  - RNA, Messenger/metabolism
MH  - Toll-Like Receptor 4/analysis
MH  - Wnt Proteins/*analysis/genetics/metabolism
MH  - Wnt-5a Protein
EDAT- 2008/05/06 09:00
MHDA- 2008/08/16 09:00
CRDT- 2008/05/06 09:00
PHST- 2008/05/06 09:00 [pubmed]
PHST- 2008/08/16 09:00 [medline]
PHST- 2008/05/06 09:00 [entrez]
AID - 00982.2007 [pii]
AID - 10.1152/ajpheart.00982.2007 [doi]
PST - ppublish
SO  - Am J Physiol Heart Circ Physiol. 2008 Jun;294(6):H2864-70. doi: 
      10.1152/ajpheart.00982.2007. Epub 2008 May 2.