title: Wnt5a, TLR2 and TLR4 are elevated in advanced human atherosclerotic lesions.
abstract: OBJECTIVE
  Atherosclerosis (ATH) is a chronic inflammatory disease that involves cascades of signaling events mediated by various effector proteins. Here we sought to determine if the expression of Wnt5a, a secreted glycoprotein, is altered in discrete regions of the arterial plaque.
  
  
  METHODS
  Atherosclerotic plaque tissues from 14 human subjects undergoing elective carotid endarterectomy were used in this study. Immunohistochemistry and laser capture microdissection combined with quantitative real-time PCR were used to determine the expression of Wnt5a and Toll-like receptors (TLRs) in different sections of the arterial lesions. Atherosclerotic serum samples (n = 30) and serum from healthy subjects (n = 16) were quantified for Wnt5a using an enzyme-linked immunosorbent assay (ELISA).
  
  
  RESULTS
  The data analysis revealed that Wnt5a transcripts and protein were elevated in advanced arterial lesions relative to less advanced arterial lesions; that Wnt5a expression correlated with the presence of TLR4 and TLR2 transcripts; and that the average amount of Wnt5a protein present in atherosclerotic patient serum was significantly higher compared to healthy controls.
  
  
  CONCLUSIONS
  This study is the first to provide evidence that the expression of Wnt5a increases as the disease progresses to a more advanced stage, and that this expression is coincident with that of TLR2 and TLR4. In addition, we found that the average Wnt5a levels in the serum of atherosclerotic patients are elevated relative to healthy controls, which is consistent with the hypothesis that Wnt5a plays a role in ATH.
authors.affiliation: Department of Biomedical Sciences, 202b Academic and Research Center, Heritage College of Osteopathic Medicine, Ohio University, Athens, OH, 45701, USA, malgor@ohio.edu.
authors.forename: Ramiro
authors.initials: R
authors.lastname: Malgor
authors.forename: Pooja M
authors.initials: PM
authors.lastname: Bhatt
authors.forename: Beth A
authors.initials: BA
authors.lastname: Connolly
authors.forename: Denise L
authors.initials: DL
authors.lastname: Jacoby
authors.forename: Kyle J
authors.initials: KJ
authors.lastname: Feldmann
authors.forename: Mitchell J
authors.initials: MJ
authors.lastname: Silver
authors.forename: Masato
authors.initials: M
authors.lastname: Nakazawa
authors.forename: Kelly D
authors.initials: KD
authors.lastname: McCall
authors.forename: Douglas J
authors.initials: DJ
authors.lastname: Goetz
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D050197:Atherosclerosis / Q000097:blood / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D002339:Carotid Arteries / Q000378:metabolism / Q000473:pathology; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D011518:Proto-Oncogene Proteins / Q000097:blood / Q000235:genetics* / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D051195:Toll-Like Receptor 2 / Q000235:genetics*; D051197:Toll-Like Receptor 4 / Q000235:genetics*; D051153:Wnt Proteins / Q000097:blood / Q000235:genetics* / Q000378:metabolism; D000071818:Wnt-5a Protein
chemical_list: D011518:Proto-Oncogene Proteins; D012333:RNA, Messenger; C495342:TLR2 protein, human; C495345:TLR4 protein, human; D051195:Toll-Like Receptor 2; D051197:Toll-Like Receptor 4; C085389:WNT5A protein, human; D051153:Wnt Proteins; D000071818:Wnt-5a Protein