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Thromb Haemost 2007; 97(02): 254-262
DOI: 10.1160/TH06-07-0373
Endothelium and Vascular Development
Schattauer GmbH

Therapeutic action of tranexamic acid in hereditary haemorrhagic telangiectasia (HHT): Regulation of ALK-1/endoglin pathway in endothelial cells

Africa Fernandez-L
1   Centro de Investigaciones Biológicas, CSIC, Ramiro de Maeztu, Madrid, Spain
,
Eva M. Garrido-Martin
1   Centro de Investigaciones Biológicas, CSIC, Ramiro de Maeztu, Madrid, Spain
,
Francisco Sanz-Rodriguez
1   Centro de Investigaciones Biológicas, CSIC, Ramiro de Maeztu, Madrid, Spain
3   Facultad de Biología, Universidad Autónoma de Madrid, Madrid, Spain
,
Jose-Ramon Ramirez
4   Anatomia Patológica, Hospital Central de la Defensa, Gomez Ulla, Spain
,
Carmelo Morales-Angulo
2   Unidad de HHT, Hospital de Sierrallana, Torrelavega, Santander, Spain
,
Roberto Zarrabeitia
2   Unidad de HHT, Hospital de Sierrallana, Torrelavega, Santander, Spain
,
Alfonso Perez-Molino
2   Unidad de HHT, Hospital de Sierrallana, Torrelavega, Santander, Spain
,
Carmelo Bernabéu
1   Centro de Investigaciones Biológicas, CSIC, Ramiro de Maeztu, Madrid, Spain
,
Luisa-María Botella
1   Centro de Investigaciones Biológicas, CSIC, Ramiro de Maeztu, Madrid, Spain
› Author Affiliations
Further Information

Publication History

Received 07 July 2006

Accepted after resubmission 10 January 2006

Publication Date:
25 November 2017 (online)

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Summary

Recurrent epistaxis is the most frequent clinical manifestation of hereditary haemorrhagic telangiectasia (HHT). Its treatment is difficult. Our objective was to assess the use of tranexamic acid (TA), an antifibrinolytic drug, for the treatment of epistaxis in HHT patients and to investigate in vitro the effects of TA over endoglin and ALK-1 expression and activity in endothelial cells. A prospective study was carried out on patients with epistaxis treated with oral TA in the HHT Unit of Sierrallana Hospital (Cantabria, Spain). Primary cultures of endothelial cells were treated with TA to measure the levels of endoglin and ALK-1 at the cell surface by flow cytometry. RNA levels were also measured by real-time PCR, and the transcriptional effects ofTA on reporters for endoglin, ALK-1 and the endoglin/ALK-1 TGF-beta pathway were assessed. The results showed that the fourteen HHT patients treated orally withTA improved, and the frequency and severity of their epistaxis were decreased. No complications derived from the treatment were observed. Cultured endothelial cells incubated with TA exhibited increased levels of endoglin and ALK-1 at the protein and mRNA levels, enhanced TGF-β signaling, and improved endothelial cell functions like tubulogenesis and migration. In summary, oral administration of TA proved beneficial for epistaxis treatment in selected patients with HHT. In addition to its already reported antifibrinolytic effects, TA stimulates the expression ofALK-1 and endoglin,as well as the activity of the ALK-1/endoglin pathway.

Keywords

Endothelial cells - HHT - endoglin - ALK-1 - tranexamic acid - fibrinolysis
 

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