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Preclinical study links gene to brain aneurysm formation

CINCINNATIUniversity of Cincinnati (UC) neurovascular researchers have identified a gene thatwhen suppressed or completely absentmay predispose a person to brain aneurysms.

Todd Abruzzo, MD, and his colleagues 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 percent of study subjects.

Scientists say this suggests that the gene may play an important role in the development of intracranial aneurysms.

An aneurysm occurs when a blood vessel weakens and stretches, forming a bulge in the vessel wall that can rupture and hemorrhage. Intracranial arterial aneurysms are bulges that develop in the arteries that carry blood to the brain.

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

When a vessel experiences increased blood flow, it attempts to reduce the shear stress to even levels by enlarging its luminal caliber through a process known as remodeling. This involves reabsorbing the inner layers of the vessel wall and forming new outer layers to replace them, explains Abruzzo.

Although we dont fully understand the genetic determinants that control an individuals susceptibility to aneurysm formation, he adds, this study is an important clue because it links a known gene with a known function to an increased risk for intracranial aneurysm formation.

Abruzzo says this study supports the idea that the NOS-3 gene is just one step in a complex molecular pathway that links flow-dependent vascular remodeling to intracranial aneurysm formation.

Our findings suggest that if something goes wrong in the vascular remodeling process, it could trigger formation of an aneurysm, he adds.

Abruzzo reports these findings in the August 2007 issu
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Contact: Amanda Harper
amanda.harper@uc.edu
513-558-4657
University of Cincinnati
7-Aug-2007


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