Infantile hemangiomas β₃-adrenoceptor overexpression is associated with nonresponse to propranolol.

Abstract

Propranolol (antagonist of β₁-/β₂-AR but minimally active against β₃-AR) is currently the first-line treatment for infantile hemangiomas (IH). Its efficacy is attributed to the blockade of β₂-AR. However, its success rate is ~60%. Considering the growing interest in the angiogenic role of β₃-ARs, we evaluated a possible relationship between β₃-AR expression and response to propranolol. 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 β₁-, β₂-, and β₃-ARs positively stained area was compared between the two groups. While no difference was found in both β₁- and β₂-AR expression level, a statistically significant increase of β₃-AR positively stained area was observed in the nonresponder group. 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 β₃-AR expression and the reduced responsiveness to propranolol treatment. This study could pave the way for new therapeutic perspectives to manage IH. Propranolol (unselective antagonist of β₁ and β₂-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 β₂-ARs. However, β₃-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 β₃-ARs in hemangioma pathogenesis and a possible new therapeutic target.