Gene Linked to Brain Aneurysms in Mice Identified

Silencing NOS-3, involved in the remodeling of blood vessels, causes formation of aneurysms.

Researchers at the University of Cincinnati (UC) demonstrated that knocking out a gene known as endothelial nitric oxide synthase (NOS-3) in an animal model led to intracranial aneurysm formation in 33% of study subjects.

Previous studies have shown that variants of the NOS-3 gene are markers for vascular disease and that the gene also plays a role in remodeling of blood vessels in response to changes in blood flow.

“Our findings suggest that if something goes wrong in the vascular remodeling process, it could trigger formation of an aneurysm,” says Todd Abruzzo, M.D., one of the authors of the study. 

The UC-led team analyzed 30 female mice bred to suppress one of three genes and molecular pathways associated with vascular disease: inducible nitric oxide synthase (NOS-2), NOS-3, or the plasminogen activator inhibitor (PAI-1).

To determine whether absence of the genes resulted in an increased rate of aneurysm formation, researchers blocked one of the two carotid arteries that carry blood to the brain. They then examined brain artery samples for signs of aneurysm formation.

They found no indications of aneurysm formation in the PAI-1, NOS-2, or wild type control groups. Mice with the NOS-3 knock-out, however, formed intracranial aneurysms.

These findings are published in the August issue of Current Neurovascular Research.