β-Adrenoceptor Blockade for Infantile Hemangioma Therapy: Do β₃-Adrenoceptors Play a Role?

Abstract

Infantile hemangiomas (IH) are frequent (4–5% of the childhood population) benign vascular tumors that involve accumulation, proliferation, and differentiation of aberrant vascular cells. Typically, IH are innocuous and spontaneously disappear, but they represent a potential risk for harmful effects in the body (e.g., permanent disfigurement) and health (e.g., ulcerations) in some patients. From a serendipitous discovery, the nonselective β-adrenoceptor blocker propranolol (which blocks β₁-adrenoceptors, β₂-adrenoceptors, and β₃-adrenoceptors) emerged as an alternative therapy to treat this pathology and it quickly became a first-line treatment for IH. Nevertheless, its specific mechanisms of action remain thus far unknown. In this respect, several studies have suggested that β₁-adrenoceptors and β₂-adrenoceptors play a role in proliferative and angiogenic mechanisms. However, current basic research studies suggest that β₃-adrenoceptors could be also involved. Notably, β₃-adrenoceptors stimulate multiple intracellular pathways related to vascular function (e.g., blood flow, angiogenesis, etc.). This review compiles some lines of evidence suggesting that β₃-adrenoceptors may: (1) play a role in the pathophysiology of IH and (2) represent a potential therapeutic target for IH treatment. Hence, clinical evidence is mandatory to decide whether incorporation of β₃-adrenoceptor blockers into the therapeutic armamentarium may increase effectiveness in the treatment of IH and other vascular anomalies.

Treatment outcomes of oral propranolol in the treatment of periocular infantile capillary hemangioma and factors predictive of recurrence and incomplete resolution: A multi-centric study

“…Response to OP based on the lesion morphology on biopsy, presence of certain receptors (GLUT-1), absence of action against β3 adrenoreceptors found in the lesion, and ultrasound and MRI characteristics of the lesion have been described in the prediction of outcome to OP. [ 4 11 12 ] Size and extent of lesion, deeper lesion due to their delayed presentation and longer proliferative phase are known to respond less, however, we found superficial lesion to be less responsive to OP, again pointing towards multiple factors which may play a role in the outcome.…”

“…Although there is significant literature on the role of propranolol and its related complications/side effects in IH affecting other parts of the body, the literature regarding periocular IH treated with OP is limited. [ 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 ] There is no definitive consensus regarding the duration of therapy as the rate of rebound growth of the lesion after stopping treatment has been reported to be 10%–30%. [ 27 28 29 ] Although the success of OP therapy is quite high, cases with no or poor response to OP after the initial few weeks have also been illustrated in the literature.…”

Can Propranolol Affect Platelet Indices in Infantile Hemangioma?

“…But there is no statistical difference between the 3 PCT values and platelet counts in both the treated and untreated group. There are different studies with PVI in cardiovascular diseases, obesity, immune thrombocytopenic purpura, atherosclerosis, and myocardial infarction, 37 but our study is the first study conducted with platelet volume indices in infantile hemangioma patients.…”

β‐Adrenoceptors as drug targets in melanoma: novel preclinical evidence for a role of β3‐adrenoceptors

“…In this respect, a recent review by Escarcega González et al . () lists some lines of evidence suggesting that β 3 ‐adrenoceptors may play a role in the pathophysiology of infantile haemangiomas thus representing a potential therapeutic target for its treatment. However, the limited pharmacological profile of the β 3 ‐adrenoceptor acting drugs currently available (see below) has hindered the translation of preclinical data to clinical outcomes, thus representing a major limiting factor for suggesting the therapeutic importance of β 3 ‐adrenoceptor blockers.…”