**5. Conclusions**

In summary, here we find that decreased levels of miRNA-370 or increased levels of miRNA-10a in plasma from HHT patients represent novel biomarkers that could help to identify undiagnosed patients within the HHT1 or HHT2 subsets, respectively. Both miRNA-370 and miRNA-10a can regulate angiogenesis, a VEGF-dependent biological process involved in the pathophysiology and therapy of HHT, by targeting, at least, VEGF receptors. Additionally, miRNA-370 and miRNA-10a are predicted to target *ENG* and *ALK1* genes, respectively, whose deleterious mutations lead to HHT1 or HHT2, respectively. These findings open up a new research avenue to better understand the functional impact of dysregulated miRNAs in HHT development. Future independent studies remain to be performed in order to further validate the role of miRNA-370 and miRNA-10a as biomarkers in HHT, as well as to investigate the functional and pathophysiological significance of these newly discovered miRNA-370/HHT1 and miRNA-10a/ALK1 associations.

**Author Contributions:** Conceptualization, L.R.-L., L.M.B., and C.B.; methodology, L.R.-L., and V.A.; software, L.R.-L., and V.A.; validation, L.R.-L.; formal analysis, L.R.-L., V.A., L.M.B., and C.B.; investigation, L.R.-L.; resources, L.M.B. and C.B.; writing—original draft preparation, L.R.-L., and C.B.; writing—review and editing, L.R.-L., V.A., L.M.B., and C.B.; visualization, L.R.-L., and C.B.; supervision and project administration, C.B.; funding acquisition, C.B.; All authors have read and agreed to the published version of the manuscript.

**Funding:** This research was funded by grants from Ministerio de Ciencia, Innovación y Universidades of Spain (SAF2013-43421-R to CB), Centro de Investigación Biomédica en Red de Enfermedades Raras (CIBERER; ISCIII-CB06/07/0038 to CB), and Consejo Superior de Investigaciones Científicas (CSIC; 201920E022 to CB). CIBERER is an initiative of the Instituto de Salud Carlos III (ISCIII) of Spain supported by European Regional Development (FEDER) funds.

**Acknowledgments:** We thank Laura Barrios (Statistics Department, Computing Center, CSIC, Madrid, Spain) for expert statistical analysis, and Carmen Langa, Elena de Blas and Lucia Recio-Poveda for technical support.

**Conflicts of Interest:** The authors declare no conflict of interest.
