title: Propranolol as antiangiogenic candidate for the therapy of hereditary haemorrhagic telangiectasia.
abstract: The β-blocker propranolol, originally designed for cardiological indications (angina, cardiac arrhythmias and high blood pressure), is nowadays, considered the most efficient drug for the treatment in infantile haemangiomas (IH), a vascular tumour that affects 5-10% of all infants. However, its potential therapeutic benefits in other vascular anomalies remain to be explored. In the present work we have assessed the impact of propranolol in endothelial cell cultures to test if this drug could be used in the vascular disease hereditary haemorrhagic telangiectasia (HHT). This rare disease is the result of abnormal angiogenesis with epistaxis, mucocutaneous and gastrointestinal telangiectases, as well as arteriovenous malformations in several organs, as clinical manifestations. Mutations in  Endoglin (ENG)  and  ACVLR1 (ALK1)  genes, lead to HHT1 and HHT2, respectively. Endoglin and ALK1 are involved in the TGF-β1 signalling pathway and play a critical role for the proper development of the blood vessels. As HHT is due to a deregulation of key angiogenic factors, inhibitors of angiogenesis have been used to normalise the nasal vasculature eliminating epistaxis derived from telangiectases. Thus, the antiangiogenic properties of propranolol were tested in endothelial cells. The drug was able to decrease cellular migration and tube formation, concomitantly with reduced RNA and protein levels of ENG and ALK1. Moreover, the drug showed apoptotic effects which could explain cell death in IH. Interestingly, propranolol showed some profibrinolytic activity, decreasing PAI-1 levels. These results suggest that local administration of propranolol in the nose mucosa to control epistaxis might be a potential therapeutic approach in HHT.
authors.affiliation: Centro de Investigaciones Biológicas, Consejo Superior de Investigaciones Científicas and Centro de Investigación Biomédica en Red de Enfermedades Raras, Madrid, Spain.
authors.forename: Virginia
authors.initials: V
authors.lastname: Albiñana
authors.forename: Lucía
authors.initials: L
authors.lastname: Recio-Poveda
authors.forename: Roberto
authors.initials: R
authors.lastname: Zarrabeitia
authors.forename: Carmelo
authors.initials: C
authors.lastname: Bernabéu
authors.forename: Luisa María
authors.initials: LM
authors.lastname: Botella
mesh_terms: D030301:Activin Receptors, Type II / Q000235:genetics / Q000378:metabolism; D000319:Adrenergic beta-Antagonists / Q000627:therapeutic use*; D020533:Angiogenesis Inhibitors / Q000627:therapeutic use*; D000818:Animals; D015703:Antigens, CD / Q000235:genetics / Q000378:metabolism; D017209:Apoptosis / Q000187:drug effects; D002460:Cell Line; D004195:Disease Models, Animal; D000071063:Endoglin; D004730:Endothelium, Vascular / Q000187:drug effects* / Q000378:metabolism; D006801:Humans; D051379:Mice; D018345:Mice, Knockout; D009154:Mutation / Q000235:genetics; D009389:Neovascularization, Pathologic / Q000188:drug therapy* / Q000235:genetics; D011433:Propranolol / Q000627:therapeutic use*; D011956:Receptors, Cell Surface / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D013683:Telangiectasia, Hereditary Hemorrhagic / Q000188:drug therapy* / Q000235:genetics
chemical_list: D000319:Adrenergic beta-Antagonists; D020533:Angiogenesis Inhibitors; D015703:Antigens, CD; C064206:ENG protein, human; D000071063:Endoglin; D011956:Receptors, Cell Surface; D011433:Propranolol; C425364:ACVRL1 protein, human; D030301:Activin Receptors, Type II