Propranolol induces regression of hemangioma cells through HIF-1α-mediated inhibition of VEGF-A

Harvey Chim, Bryan S. Armijo, Erin Miller, Christy Gliniak, Marc A. Serret, Arun K. Gosain*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

115 Scopus citations


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.

Original languageEnglish (US)
Pages (from-to)146-156
Number of pages11
JournalAnnals of surgery
Issue number1
StatePublished - Jul 2012

ASJC Scopus subject areas

  • Surgery


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