A non-genetic model of vascular shunts informs on the cellular mechanisms of formation and resolution of arteriovenous malformations.

ABSTRACT:

Aims

Arteriovenous malformations (AVMs), a disorder characterized by direct shunts between arteries and veins, are associated with genetic mutations. However, the mechanisms leading to AV shunt formation and how shunts can be reverted are poorly understood.

Methods and results

Here, we report that oxygen-induced retinopathy (OIR) protocol leads to the consistent and stereotypical formation of AV shunts in non-genetically altered mice. OIR-induced AV shunts show all the canonical markers of AVMs. Genetic and pharmacological interventions demonstrated that changes in the volume of venous endothelial cells (EC)-hypertrophic venous cells-are the initiating step promoting AV shunt formation, whilst EC proliferation or migration played minor roles. Inhibition of the mTOR pathway p

SUBMITTER: Ouarne M 

PROVIDER: S-EPMC11629978 | biostudies-literature | 2024 Dec

REPOSITORIES: biostudies-literature