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.