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

J Vasc Res. 2018;55(3):159-168. doi: 10.1159/000489956. Epub 2018 Jun 22.

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.

Keywords: Blood flow; Infantile hemangioma; Propranolol; β3-Adrenoceptors.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Adrenergic beta-3 Receptor Antagonists / adverse effects
  • Adrenergic beta-3 Receptor Antagonists / therapeutic use*
  • Animals
  • Antineoplastic Agents / adverse effects
  • Antineoplastic Agents / therapeutic use*
  • Hemangioma, Capillary / drug therapy*
  • Hemangioma, Capillary / metabolism
  • Hemangioma, Capillary / pathology
  • Humans
  • Neoplastic Syndromes, Hereditary / drug therapy*
  • Neoplastic Syndromes, Hereditary / metabolism
  • Neoplastic Syndromes, Hereditary / pathology
  • Neovascularization, Pathologic*
  • Receptors, Adrenergic, beta-3 / drug effects*
  • Receptors, Adrenergic, beta-3 / metabolism
  • Signal Transduction / drug effects
  • Treatment Outcome

Substances

  • ADRB3 protein, human
  • Adrenergic beta-3 Receptor Antagonists
  • Antineoplastic Agents
  • Receptors, Adrenergic, beta-3

Supplementary concepts

  • Hemangioma, capillary infantile