Page 55 - CIBERER2016-ENG

Most relevant scientific articles
• Gallardo-Vara E., Blanco F.J., Roque M., Friedman S.L., Suzuki T., Botella L.M. et al. Transcription factor KLF6 upregulates expression of metalloprotease MMP14 and subsequent release of soluble endoglin during vascular injury. Angiogenesis. 2016;1-17.
• Ojeda-Fernandez L., Recio-Poveda L., Aristorena M., Lastres P., Blanco F.J., Sanz-Rodriguez F. et al. Mice Lacking Endoglin in Macrophages Show an Impaired Immune Response. PLoS Genetics. 2016;12(3).
• Parra J.A., Cuesta J.M., Zarrabeitia R., Farinas-Alvarez C., Bueno J., Marques S. et al. Screening pulmonary arteriovenous malformations in a large cohort of Spanish patients with hemorrhagic hereditary telangiectasia. International Journal of Cardiology. 2016; 218:240-245.
• Zarrabeitia R., Ojeda-Fernandez L., Recio L., Bernabeu C., Parra J.A., Albinana V. et al. Bazedoxifene, a new orphan drug for the treatment of bleeding in hereditary haemorrhagic telangiectasia. Thrombosis and Haemostasis. 2016;115(6):1167-1177.
• Nunez-Gomez E., Pericacho M., Ollauri-Ibanez C., Bernabeu C., Lopez-Novoa J.M. The role of endoglin in post-ischemic revascularization. Angiogenesis. 2016;1-24.
Hightlights
Immune system response is affected in HHT patients. This is a new clinical aspect of this multisystemic vascular dysplasia. These results have been reported in a myeloid-lineage specific eng KO murine model, developed in our group. Clinical consequences derived of these results are directly in line with the prevention/treatment of rare infections, nosocomial infections, brain abscesses and sepsis developed
by HHT patients. The molecular basis of bazedoxifene action as therapeutic drug in HHT, together with a pilot study with 5 HHT patients, has been described in a comprehensive manner. The content of this work is the support for the 2nd orphan designation for HHT obtained from EMA by the end of 2014. The direct cooperation with clinicians from Sierrallana/Valdecilla clinicians has led to a papers in a large cohort
of HHT Spanish patients, from which we get samples to study biomarkers: miRNAs, growth factors and cytokines.
The wound healing molecular basis are studied in vessels and endothelial cells. Actors of the process are membrane endoglin, MMP14 and the endoglin soluble form release, and the role played in angiogenesis and vascular repair. All this process is orchestrated by KLF6 as a master transcription factor and in relation to HHT situations.
Endoglin is being studied in other pathologies related with hemostasis and kidney fibrosis.
A new designation of orphan drug has been applied for propranolol in Von Hippel Lindau disease, to EMA. The answer was positive at the COMP meeting of January 19th 2017. A protocol for a pilot clinical trial in HHT, was presented to AEMPs to start presumably this year 2017, after approval.
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research groups 55