Infantile hemangiomas β 3 -adrenoceptor overexpression is associated with nonresponse to propranolol.

Background: Propranolol (antagonist of β ₁ -/β ₂ -AR but minimally active against β ₃ -AR) is currently the first-line treatment for infantile hemangiomas (IH). Its efficacy is attributed to the blockade of β ₂ -AR. However, its success rate is ~60%. Considering the growing interest in the angiogenic role of β ₃ -ARs, we evaluated a possible relationship between β ₃ -AR expression and response to propranolol.
Methods: Fifteen samples of surgical biopsies were collected from patients with IH. Three were taken precociously from infants and then successfully treated with propranolol (responder group). Twelve were taken later, from residual lesions noncompletely responsive to propranolol (nonresponder group). A morphometrical analysis of the percentage of β ₁ -, β ₂ -, and β ₃ -ARs positively stained area was compared between the two groups.
Results: While no difference was found in both β ₁ - and β ₂ -AR expression level, a statistically significant increase of β ₃ -AR positively stained area was observed in the nonresponder group.
Conclusions: Although the number of biopsies is insufficient to draw definitive conclusions, and the different β-AR pattern may be theoretically explained by the different timing of samplings, this study suggests a possible correlation between β ₃ -AR expression and the reduced responsiveness to propranolol treatment. This study could pave the way for new therapeutic perspectives to manage IH.
Impact: Propranolol (unselective antagonist of β ₁ and β ₂ -ARs) is currently the first-line treatment for IHs, with a success rate of ~60%. Its effectiveness has been attributed to its ability to block β ₂ -ARs. However, β ₃ -ARs (on which propranolol is minimally active) were significantly more expressed in hemangioma biopsies taken from patients nonresponsive to propranolol. This study suggests a possible role of β ₃ -ARs in hemangioma pathogenesis and a possible new therapeutic target.
(© 2021. The Author(s), under exclusive licence to the International Pediatric Research Foundation, Inc.)