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.
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.
Black men appear less likely to undergo elective aneurysm repair than white men
Black men are less likely than white men to undergo elective surgery to repair abdominal aortic aneurysms, even after accounting for racial differences in rates of developing the disease, according to a report in the May issue of Archives of Surgery.
The Medical Minute--What is vascular disease?
In simplest terms, “vascular” is a word that refers to blood vessels, those little tubes called arteries and veins that carry blood throughout the body. Health professionals often describe blood vessels based on their location, such as cardiovascular (heart), cerebrovascular (brain), and peripheral vascular (all the other vessels in the body). The most common diseases of veins are varicose veins and venous thrombosis (clots), which range in severity.
Smokers treated for brain aneurysm with coils at higher risk of recurrence
Cigarette smokers who were treated for cerebral aneurysms with coil embolization (blocking of a blood vessel) are at greater risk of developing another aneurysm, say neurological surgeons at Jefferson Hospital for Neuroscience in Philadelphia in the first-known study of its kind.
New devices less effective in thwarting brain aneurysm recurrence
A retrospective analysis of 100 patients suffering from a ruptured brain aneurysm has found that expensive new coiling devices are no more effective than bare platinum coils at preventing aneurysms from recurring.
Half of patients undergoing cerebrovascular stent placement respond poorly to clopidogrel
A study by researchers at Rush University Medical Center, published in the February issue of the American Journal of Neuroradiology, finds that half of patients undergoing cerebrovascular stent placement did not respond well to clopidogrel. Clopidogrel (Plavix) and aspirin are medications routinely prescribed for 1-3 months following cerebrovascular stent placement to combat the risk of blood clots (stent-thrombosis) and reclosure of the artery (re-stenosis).

News discussion:

Medicine & Health news