Introduction: HHT type 2 (HHT2) is an autosomal dominant inherited disease in which one allele of the ACVRL1 gene is mutant. Patients have severe disturbances in angiogenesis and clinically often present with severe nosebleeds and an impaired quality of life. The aim of our study was to investigate how overexpression of ACVRL1 in the endothelial cell line HMEC-1 affects angiogenesis. Material and methods: Overexpression of wild type ACVRL1 was achieved after transfecting a wild type ACVRL1-encoding plasmid into HMEC-1 cells. Quantitative PCR was used to assess gene expression levels. Expression of the ACVRL1 protein was evaluated by fluorescence microscopy. The consequences of ACVRL1 overexpression were evaluated using a Matrigel-based tube formation assay. Tube formation was quantified with the Angiogenesis Analyzer software (ImageJ, Fiji). Results: Significant (p<0.05) ACVRL1 overexpression in HMEC-1 cells was achieved at the nucleic acid level and was confirmed by RT-qPCR. Overexpression of the ACVRL1 protein was demonstrated by immunofluorescence microscopy. Angiogenesis analysis after ACVRL1 overexpression revealed a significantly lower number of vessel junctions, greater segment lengths and more isolated segments. Conclusion/Discussion: Overexpression of wild type ACVRL1 in HMEC-1 cells inhibits their angiogenic ability. It leads to a significant reduction in vessel formation, which is opposite to the enhanced vessel production as seen in HHT2 patients which carry a mutant ACVRL1 allele that gives rise to an inactive ACVRL1 protein. Future studies need to assess if overexpression of wild type ACVRL1 in HHT2 endothelial cells, that are haploinsufficient for ACVRL1, could help to alleviate the symptoms of HHT2 patients by normalizing angiogenesis.

Die Autorinnen/Autoren geben an, dass kein Interessenkonflikt besteht.