| Propranolol Induces Regression of Hemangioma Cells Through HIF-1α-Mediated Inhibition of VEGF-A. | |
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MedLine Citation:
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PMID: 22580939 Owner: NLM Status: Publisher |
Abstract/OtherAbstract:
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OBJECTIVE:: To investigate the mechanism of propranolol on regression of infantile hemangiomas. BACKGROUND:: Propranolol has been found to be effective in treatment of severe hemangiomas of infancy. However, its mechanism of action is as yet unknown. METHODS:: Cultured proliferating and involuting hemangioma endothelial cells were treated with varying concentrations of propranolol for up to 4 days. Analysis was performed using cell viability, migration, and tubulogenesis assays, as well as quantitative RT-PCR and flow cytometry. Western blots and ELISA assays were used to assess protein expression. RESULTS:: Treatment with propranolol led to a dose dependent cytotoxic effect in hemangioma endothelial cells with decreased cell viability, migration, and tubulogenesis. This cytotoxic effect was VEGF (vascular endothelial growth factor) dependent, as demonstrated by decreased VEGF, VEGF-R1, and VEGF-R2 production. Decreased signaling through the VEGF pathway resulted in downregulation of PI3/Akt and p38/MAPK activity. Decreased VEGF activity was mediated through the hypoxia inducible factor (HIF)-1α pathway but not through NF-κβ signaling. CONCLUSIONS:: Collectively, these data suggest that propranolol exerts its suppressive effects on hemangiomas through the HIF-1α-VEGF-A angiogenesis axis, with effects mediated through the PI3/Akt and p38/MAPK pathways. These findings provide a plausible mechanism of action of propranolol on regression of infantile hemangiomas. |
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Authors:
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Harvey Chim; Bryan S Armijo; Erin Miller; Christy Gliniak; Marc A Serret; Arun K Gosain |
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Publication Detail:
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Type: JOURNAL ARTICLE Date: 2012-5-10 |
Journal Detail:
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Title: Annals of surgery Volume: - ISSN: 1528-1140 ISO Abbreviation: - Publication Date: 2012 May |
Date Detail:
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Created Date: 2012-5-14 Completed Date: - Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 0372354 Medline TA: Ann Surg Country: - |
Other Details:
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Languages: ENG Pagination: - Citation Subset: - |
Affiliation:
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From the Department of Plastic Surgery, Case Western Reserve University, Cleveland, OH. |
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From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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