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

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.