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: Luca Filippi, Massimo Dal Monte, Giovanni Casini, Marta Daniotti, Federica Sereni, Paola Bagnoli
• Journal: Medicinal research reviews (Med Res Rev) Vol. 35 Issue 3 Pg. 619-52 (May 2015) ISSN: 1098-1128 [Electronic] United States
• PMID: 25523517 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Review)
• Copyright: © 2014 Wiley Periodicals, Inc.

Chemical References

• Adrenergic beta-Antagonists
• Receptors, Adrenergic, beta
• Nitric Oxide
• Propranolol

Topics

• Adrenergic beta-Antagonists (therapeutic use)
• Animals
• Cell Line, Tumor
• Child, Preschool
• Hemangioma (complications, metabolism)
• Humans
• Hypoxia
• Infant
• Mice
• Neoplasms (complications, metabolism)
• Nitric Oxide (chemistry)
• Propranolol (therapeutic use)
• Receptors, Adrenergic, beta (metabolism)
• Retinal Diseases (complications, metabolism)
• Retinopathy of Prematurity (complications, metabolism)