Infantile Hemangiomas, Retinopathy of Prematurity and Cancer: A Common Pathogenetic Role of the β-Adrenergic System

The serendipitous demonstration that the nonselective -adrenergic receptor (-AR) antagonist propranolol promotes the regression of infantile hemangiomas (IHs) aroused interest around the involvement of the -adrenergic system in angiogenic processes. The efficacy of propranolol was related to the (2)-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 (3)-ARs in the development of ROP and, together with several preclinical studies demonstrating the key role of the -adrenergic system in tumor progression, vascularization, and metastasis, prompted us to also investigate the participation of (3)-ARs in tumor growth. The aim of this review is to gather the recent findings on the role of the -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 -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 -ARs in diseases characterized by chronic hypoxia may come from research focusing on the fetal and neonatal period.