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This Article Full Text Full Text (PDF) All Versions of this Article: 294/6/H2864    most recent 00982.2007v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Web of Science (2) Citing Articles via Google Scholar Google Scholar Articles by Christman, M. A. Articles by Malgor, R. Search for Related Content PubMed PubMed Citation Articles by Christman, M. A., II Articles by Malgor, R.

Wnt5a is expressed in murine and human atherosclerotic lesions

¹Department of Chemical and Biomolecular Engineering, Ohio University, ²Mid West Cardiology Research Foundation, Columbus, Ohio, ³Edison Biotechnology Institute, Ohio University, ⁴Department of Biomedical Sciences, College of Osteopathic Medicine, Ohio University, ⁵Department of Specialty Medicine, Ohio University, and ⁶Department of Biological Sciences, Molecular and Cellular Biology Graduate Program, Ohio University, Athens, OH

Submitted 24 August 2007 ; accepted in final form 22 April 2008

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.

atherosclerosis; inflammation; macrophage; Toll-like receptor; Wnt

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