Endoglin prevents vascular malformation by regulating flow-induced cell migration and specification through VEGFR2 signalling.

Loss-of-function (LOF) mutations in the endothelial cell (EC)-enriched gene endoglin (ENG) cause the human disease hereditary haemorrhagic telangiectasia-1, characterized by vascular malformations promoted by vascular endothelial growth factor A (VEGFA). How ENG deficiency alters EC behaviour to trigger these anomalies is not understood. Mosaic ENG deletion in the postnatal mouse rendered Eng LOF ECs insensitive to flow-mediated venous to arterial migration. Eng LOF ECs retained within arterioles acquired venous characteristics and secondary ENG-independent proliferation resulting in arteriovenous malformation (AVM). Analysis following simultaneous Eng LOF and overexpression (OE) revealed that ENG OE ECs dominate tip-cell positions and home preferentially to arteries. ENG knockdown altered VEGFA-mediated VEGFR2 kinetics and promoted AKT signalling. Blockage of PI(3)K/AKT partly normalized flow-directed migration of ENG LOF ECs in vitro and reduced the severity of AVM in vivo. This demonstrates the requirement of ENG in flow-mediated migration and modulation of VEGFR2 signalling in vascular patterning.

7-day weighed food diaries suggest patients with hereditary hemorrhagic telangiectasia may spontaneously modify their diet to avoid nosebleed precipitants.

Hereditary hemorrhagic telangiectasia (HHT) poses substantial burdens due to nosebleeds and iron deficiency resulting from recurrent hemorrhagic iron losses. Recent studies by our group found surprising links between HHT nosebleeds and certain food groups. In this letter, we report 7-day weighed food diary assessments of an unselected group of 25 UK patients with HHT whose nosebleeds ranged from mild to severe (median epistaxis severity score 4.66, range 0.89- 9.11). The diaries provide evidence that food items most commonly reported to provoke nosebleeds were ingested by fewer HHT patients, compared to food items less commonly reported to provoke nosebleeds (chi-squared p <0.001).

Epistaxis in hereditary haemorrhagic telangiectasia.

Hereditary haemorrhagic telangiectasia (HHT) is characterized by easily bleeding telangiectases of the skin and mucosa. Epistaxis is the most common symptom of HHT. Larger arteriovenous malformations (AVM) occur in the lungs (in up to 33% of the patients), brain (in up to 11% of patients), and liver. These may cause severe complications which can be prevented by early therapy. To gain insight in the characteristics of epistaxis in HHT, 171 persons were investigated, who either had HHT or participated in a screening programme for relatives of HHT patients. Of these, 58 persons had HHT. Epistaxis without signs of HHT was present in 12 persons, whereas 10% of HHT patients did not have epistaxis. Seventeen HHT patients with epistaxis had visited an otorhinolaryngologist before, without a correct diagnosis of HHT being made. Telangiectases were most common on lips, tongue, the nasal septum, and the turbinates. In view of the prevalence of visceral AVM and the associated complications, HHT patients presenting to an otorhinolaryngologist should be encouraged to engage in a screening programme for these AVM.