Genetic and pharmacological targeting of mTORC1 in mouse models of arteriovenous malformation expose non-cell autonomous signalling in HHT.

ABSTRACT: Arteriovenous malformations (AVMs) are abnormal high flow shunts between arteries and veins with major negative impact on the cardiovascular system. Inherited loss-of-function (LOF) mutations in endoglin, encoding an endothelial cell (EC) expressed co-receptor for BMP9/10, causes the disease HHT1/Osler-Weber-Rendu, characterized by bleeding and AVMs. Here we observe increased activity of the downstream signalling complex mTORC1 within the retinal vasculature of HHT mouse models. To investigate its importance in AVM biology, concerning subvascular action, cell specificity, signalling strength and kinetics we combine timed genetic and antibody-based models of HHT with genetic mTORC1 inhibition or activation through EC specific deletion of Rptor or Tsc1. Results demonstrate that EC mTORC1 act

SUBMITTER: Queiro-Palou A 

PROVIDER: S-EPMC11634917 | biostudies-literature | 2024 Dec

REPOSITORIES: biostudies-literature