Vascular Anomalies and Treatments

Gene-specific endothelial programs drive AVM pathogenesis in SMAD4 and ALK1 loss-of-function

This study identifies gene-specific mechanisms of AVM formation in endothelial cells with SMAD4 or ALK1 loss-of-function, showing distinct molecular and cellular pathways leading to different vascular malformations.

An angiopoietin-2 vaccine improves arteriovenous malformation pathology in hereditary hemorrhagic telangiectasia mice

A peptide vaccine targeting ANG2 reduces AVM number and size and normalizes vascular diameters in HHT mice without causing organ dysfunction.

Hereditary hemorrhagic telangiectasia prevalence estimates calculated from gnomAD allele frequencies of predicted pathogenic variants in ENG and ACVRL1

The paper estimates HHT prevalence using gnomAD variant frequencies and three methods, finding it 2-12 times higher than current estimates.

PIEZO1 overexpression in hereditary hemorrhagic telangiectasia arteriovenous malformations

The paper identifies PIEZO1 overexpression in HHT2 AVMs and shows that inhibiting PIEZO1 reduces AVM formation in Alk1-deficient mice.

Blood flow regulates acvrl1 transcription via ligand-dependent Alk1 activity

The paper shows that blood flow and Bmp10 regulate acvrl1 transcription in zebrafish and human endothelial cells through Alk1 signaling.

Novel uAUG creating variants in the 5UTR of ENG causing Hereditary Hemorrhagic Telangiectasia

This paper identifies two novel 5UTR ENG variants in HHT patients that create uAUGs, leading to uoORFs and reduced ENG protein levels and function.

Endoglin deficiency elicits hypoxia-driven congestive heart failure in zebrafish.

This study shows that endoglin deficiency in zebrafish causes hypoxia-driven heart failure and anemia, mirroring features of Hereditary Hemorrhagic Telangiectasia (HHT).

Arterial endoglin does not protect against arteriovenous malformations

The paper shows that arterial endoglin (ENG) is not necessary to prevent arteriovenous malformations (AVMs), as specific loss of ENG in venous and capillary endothelium resulted in AVM frequency similar to pan-endothelial loss.

Somatic Mutations in Vascular Malformations of Hereditary Hemorrhagic Telangiectasia Result in Biallelic Loss of ENG or ACVRL1

The paper identifies biallelic loss of ENG or ACVRL1 through somatic mutations in HHT-related telangiectasia, supporting a two-hit mechanism over haploinsufficiency.