| Inhibition of canonical Wnt signaling increases microvascular hemorrhaging and venular remodeling in adult rats. | |
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MedLine Citation:
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PMID: 20618692 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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OBJECTIVE: The canonical Wnt signaling pathway, heavily studied in development and cancer, has recently been implicated in microvascular growth with the use of developmental and in vitro models. To date, however, no study exists showing the effects of perturbing the canonical Wnt pathway in a complete microvascular network undergoing physiological remodeling in vivo. Our objective was to investigate the effects of canonical Wnt inhibition on the microvascular remodeling of adult rats. METHODS: Canonical Wnt inhibitor DKK-1, Wnt inhibitor sFRP-1, BSA or saline was superfused onto the exteriorized mesenteric windows of 300 g adult female Sprague-Dawley rats for 20 minutes. Three days following surgery, mesenteric windows were imaged intravitally and harvested for immunofluorescence staining with smooth muscle alpha-actin and BRDU. RESULTS: We observed prominent differences in the response of the mesenteric microvasculature amongst the various treatment groups. Significant increases in hemorrhage area, vascular density, and draining vessel diameter were observed in windows treated with Wnt inhibitors as compared to control-treated windows. Additionally, confocal imaging analysis showed significant increases in proliferating cells as well as evidence of proliferating smooth muscle cells along venules. CONCLUSIONS: Together, our results suggest that canonical Wnt inhibition plays an important role in microvascular remodeling, specifically venular remodeling. |
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Authors:
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Jason T Glaw; Thomas C Skalak; Shayn M Peirce |
Publication Detail:
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Type: Journal Article; Research Support, N.I.H., Extramural |
Journal Detail:
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Title: Microcirculation (New York, N.Y. : 1994) Volume: 17 ISSN: 1549-8719 ISO Abbreviation: Microcirculation Publication Date: 2010 Jul |
Date Detail:
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Created Date: 2010-07-12 Completed Date: 2010-10-29 Revised Date: 2011-08-01 |
Medline Journal Info:
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Nlm Unique ID: 9434935 Medline TA: Microcirculation Country: United States |
Other Details:
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Languages: eng Pagination: 348-57 Citation Subset: IM |
Affiliation:
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Department of Biomedical Engineering, University of Virginia, Charlottesville, Virginia 22908, USA. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Animals Cell Proliferation / drug effects Female Hemorrhage / etiology*, pathology, physiopathology Intercellular Signaling Peptides and Proteins / pharmacology, physiology Membrane Proteins / pharmacology, physiology Mesenteric Veins / drug effects, pathology, physiopathology Microcirculation / drug effects, physiology* Models, Cardiovascular Neovascularization, Physiologic / drug effects Rats Rats, Sprague-Dawley Recombinant Proteins / pharmacology Signal Transduction / drug effects Venules / drug effects, pathology, physiopathology Wnt Proteins / antagonists & inhibitors*, physiology |
| Grant Support | |
ID/Acronym/Agency:
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5R01HL082838-03/HL/NHLBI NIH HHS; HL065958/HL/NHLBI NIH HHS; R01 HL082838-04/HL/NHLBI NIH HHS; R01 HL082838-05/HL/NHLBI NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/Intercellular Signaling Peptides and Proteins; 0/Membrane Proteins; 0/Recombinant Proteins; 0/Sfrp1 protein, rat; 0/Wnt Proteins; 0/dickkopf-1 protein, rat |
| Comments/Corrections | |
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