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Thromb Haemost 2012; 108(01): 41-53
DOI: 10.1160/TH11-11-0809
Blood Coagulation, Fibrinolysis amd Cellular Haemostasis
Schattauer GmbH

Propranolol as antiangiogenic candidate for the therapy of hereditary haemorrhagic telangiectasia

Virginia Albiñana
1   Centro de Investigaciones Biológicas (CIB), Consejo Superior de Investigaciones Científicas (CSIC) and Centro de Investigación Biomédica en Red de Enfermedades Raras (CIBERER), Madrid, Spain
,
Lucía Recio-Poveda
1   Centro de Investigaciones Biológicas (CIB), Consejo Superior de Investigaciones Científicas (CSIC) and Centro de Investigación Biomédica en Red de Enfermedades Raras (CIBERER), Madrid, Spain
,
Roberto Zarrabeitia
2   Hospital Sierrallana, Centro de Referencia HHT, Torrelavega, Cantabria, Spain
,
Carmelo Bernabéu
1   Centro de Investigaciones Biológicas (CIB), Consejo Superior de Investigaciones Científicas (CSIC) and Centro de Investigación Biomédica en Red de Enfermedades Raras (CIBERER), Madrid, Spain
,
Luisa María Botella
1   Centro de Investigaciones Biológicas (CIB), Consejo Superior de Investigaciones Científicas (CSIC) and Centro de Investigación Biomédica en Red de Enfermedades Raras (CIBERER), Madrid, Spain
› Author Affiliations Financial support: This work was supported by the Ministerio de Ciencia e Innovacion [Grants SAF2008–01218, SAF2007–61827, and SAF2010–19222] and Fundación Ramón Areces of Spain (Rare and Emergent Diseases). CIBERER is an initiative of the Instituto de Salud Carlos III (ISCIII) of Spain.
Further Information

Publication History

Received: 24 November 2011

Accepted after major revision: 01 April 2012

Publication Date:
22 November 2017 (online)

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Summary

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.

Keywords

Propranolol - HHT - endoglin - ALK1 - epistaxis
 

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