Preclinical study links gene to brain aneurysm formation

University of Cincinnati (UC) neurovascular researchers have identified a gene that—when suppressed or completely absent—may 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 don’t fully understand the genetic determinants that control an individual’s 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 issue of Current Neurovascular Research.

The UC-led team analyzed 30 female mice bred to suppress (knock out) one of three genes and molecular pathways associated with vascular disease: inducible nitric oxide synthase (NOS-2), endothelial nitric oxide synthase (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.

The researchers 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.

Source: University of Cincinnati

Related stories:

Life-threatening gene defect located by UT-Houston researchers
A research team led by scientists at The University of Texas Medical School at Houston has identified a defective gene that affects vascular smooth-muscle cells in people who suffer from hereditary thoracic aortic disease, which can kill victims with little warning in the prime of their lives.
Adults with aortic valve disorder do not experience reduction in survival rate
Young adults with a bicuspid aortic valve, a congenital heart abnormality, experience subsequent cardiac events but do not appear to have lower survival rates compared to the general population, according to a study in the September 17 issue of JAMA.
At risk for peripheral arterial disease? Simple quiz provides key so you can circulate better
Ten million Americans have peripheral arterial disease (PAD), and research shows that the highest risk populations include African-Americans (twice as likely to develop clogged leg arteries), seniors (12-20 percent develop PAD) and diabetics (one in three who are over the age of 50 develop PAD). Legs for Life®—a community health and public information program—recommends that older Americans take its free, online self-assessment quiz.
Tiny 3-D ultrasound probe guides catheter procedures
An ultrasound probe small enough to ride along at the tip of a catheter can provide physicians with clearer real-time images of soft tissue without the risks associated with conventional x-ray catheter guidance.
More aortic chest aneurysms being treated with less-invasive stents
An estimated 60,000 Americans are walking around with time bombs in their chests called thoracic aortic aneurysms. At any time, their main chest artery could suddenly burst open, causing massive internal bleeding that is almost always fatal.
Brain surgery is getting easier on patients
Dr. Edward Duckworth is part of a new generation of neurosurgeons who are making brain surgery a lot easier on patients. At Loyola University Hospital, Duckworth is using less-invasive techniques to remove tumors, to repair life-threatening aneurysms and to dramatically reduce seizures in epilepsy patients.
Women, Mexican-Americans at higher risk of ruptured brain aneurysm
A type of stroke that can strike at any age, and kills one-third of its victims, appears to be more common in women and Mexican-Americans than in non-Hispanic white men, according to a new study from the University of Michigan Stroke Program.
Preserving skin elasticity could unlock secrets for better body health
University of Manchester scientists have begun a study to understand the decline of ‘springiness’ in our bodies' skin and tissues as we get older.

News discussion:

Medicine & Health news