title: Infantile hemangiomas, retinopathy of prematurity and cancer: a common pathogenetic role of the β-adrenergic system.
abstract: The serendipitous demonstration that the nonselective β-adrenergic receptor (β-AR) antagonist propranolol promotes the regression of infantile hemangiomas (IHs) aroused interest around the involvement of the β-adrenergic system in angiogenic processes. The efficacy of propranolol was related to the β2-AR blockade and the consequent inhibition of the production of vascular endothelial growth factor (VEGF), suggesting the hypothesis that propranolol could also be effective in treating retinopathy of prematurity (ROP), a retinal pathology characterized by VEGF-induced neoangiogenesis. Consequent to the encouraging animal studies, a pilot clinical trial showed that oral propranolol protects newborns from ROP progression, even though this treatment is not sufficiently safe. Further, animal studies clarified the role of β3-ARs in the development of ROP and, together with several preclinical studies demonstrating the key role of the β-adrenergic system in tumor progression, vascularization, and metastasis, prompted us to also investigate the participation of β3-ARs in tumor growth. The aim of this review is to gather the recent findings on the role of the β-adrenergic system in IHs, ROP, and cancer, highlighting the fact that these different pathologies, triggered by different pathogenic noxae, share common pathogenic mechanisms characterized by the presence of hypoxia-induced angiogenesis, which may be contrasted by targeting the β-adrenergic system. The mechanisms characterizing the pathogenesis of IHs, ROP, and cancer may also be active during the fetal-neonatal development, and a great contribution to the knowledge on the role of β-ARs in diseases characterized by chronic hypoxia may come from research focusing on the fetal and neonatal period.
authors.affiliation: Neonatal Intensive Care Unit, Medical Surgical Fetal-Neonatal Department, "A. Meyer" University Children's Hospital, Florence, Italy.
authors.forename: Luca
authors.initials: L
authors.lastname: Filippi
authors.forename: Massimo
authors.initials: M
authors.lastname: Dal Monte
authors.forename: Giovanni
authors.initials: G
authors.lastname: Casini
authors.forename: Marta
authors.initials: M
authors.lastname: Daniotti
authors.forename: Federica
authors.initials: F
authors.lastname: Sereni
authors.forename: Paola
authors.initials: P
authors.lastname: Bagnoli
mesh_terms: D000319:Adrenergic beta-Antagonists / Q000627:therapeutic use; D000818:Animals; D045744:Cell Line, Tumor; D002675:Child, Preschool; D006391:Hemangioma / Q000150:complications / Q000378:metabolism*; D006801:Humans; D000860:Hypoxia; D007223:Infant; D051379:Mice; D009369:Neoplasms / Q000150:complications / Q000378:metabolism*; D009569:Nitric Oxide / Q000737:chemistry; D011433:Propranolol / Q000627:therapeutic use; D011943:Receptors, Adrenergic, beta / Q000378:metabolism*; D012164:Retinal Diseases / Q000150:complications / Q000378:metabolism; D012178:Retinopathy of Prematurity / Q000150:complications / Q000378:metabolism*
chemical_list: D000319:Adrenergic beta-Antagonists; D011943:Receptors, Adrenergic, beta; D009569:Nitric Oxide; D011433:Propranolol
keywords: beta blockers; cancer; propranolol; retinal diseases; retinal neovascularization