Abstract
Propranolol is a widely used beta blocker that consists of a racemic mixture of R and S stereoisomers. Only the S stereoisomer has significant activity against the beta-adrenergic receptor. A fortuitous clinical observation was made in an infant who received propranolol for cardiac disease, and regression of a hemangioma of infancy was noted. This has led to the widespread use of propranolol for the treatment of large and life-threatening hemangiomas of infancy. Infants receiving propranolol require monitoring to ensure that they do not suffer from side effects related to beta blockade. The exact mechanism of activity of propranolol in hemangioma of infancy is unknown. In this study, we treated hemangioma stem cells with both beta blockade active S- and inactive R-propranolol and looked for genes that were coordinately regulated by this treatment. Among the genes commonly downregulated, Angiopoietin-like 4 (ANGPTL4) was among the most regulated. We confirmed that propranolol isomers downregulated ANGPTL4 in endothelial cells, with greater downregulation of ANGPTL4 using the beta blockade inactive R-propranolol. ANGPTL4 is present in human hemangiomas of infancy. Finally, R-propranolol inhibited the growth of bEnd.3 hemangioma cells in vivo. The implication of this is that hemangioma growth can be blocked without the side effects of beta blockade. Given that humans have been exposed to racemic propranolol for decades and thus to R-propranolol, clinical development of R-propranolol for hemangiomas of infancy and other angiogenic diseases is warranted.
Highlights
Hemangiomas of infancy represent the most common childhood neoplasm
We further investigated the effect of beta blockade negative R-propranolol in a murine model of hemangioma of infancy and found that it is effective in tumor reduction
R-isomer of propranolol reduces the expression of Angiopoietin-like 4 (ANGPTL4) in hemangiomas of infancy
Summary
Hemangiomas of infancy represent the most common childhood neoplasm. These lesions occur in up to 10% of infants, with a female predominance and a higher incidence in premature infants.[1]. We treated human endothelial stem cells derived from hemangiomas of infancy with R- and S-propranolol and found that R-propranolol was more effective in downregulating one of the factors in IH. R-propranolol is effective in reducing tumor volume in vivo against bEnd.[3] cells, a murine model of hemangioma of infancy.[15,17] Our results suggest that beta blockade is not required for the effect of propranolol for
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
