Gene Discovery Could Lead to New Stroke Treatments

In Study, Gene 'Signature' Linked to Unstable Plaque Associated With Strokes

By Salynn Boyles
WebMD Health News

Reviewed by Laura J. Martin, MD

Aug. 4, 2011 -- Plaque buildup in the arteries is a major risk factor for strokes and heart attack, but some plaques are far more dangerous than others.

The problem is there is no good way to distinguish relatively benign plaque on artery walls from plaque that will break off and cause harm, but that may soon change.

Researchers in Italy say they have identified a genetic "signature" seen in unstable plaque from patients who had a stroke, but not in plaque that is not likely to rupture.

If the findings from the small study are confirmed, the discovery could lead to better ways to identify people with clogged arteries at risk for stroke and even new treatments to prevent and treat artery disease.

The study was reported today in the online issue of the American Heart Association journal Stroke.

Plaque Rupture Major Cause of Stroke

Arterial plaque is made up of a combination fat, cholesterol, calcium, and other substances found in the blood that cling to the inner walls of the arteries.

As plaque deposits get bigger, the arteries become narrow and cut off blood to the brain or heart. Although this narrowing alone causes some heart attacks and strokes, many more are caused when plaque breaks off or ruptures, blocking the flow of blood through the arteries that lead to the heart and brain.

Many experts now believe that the inability to distinguish between stable and unstable plaques in the clinical setting has led to the overuse of treatments to clear blocked arteries.

In the Italian study, Cipollone and colleagues examined the expression of microRNAs in plaque taken from the carotid arteries of people who had recently had strokes and people with carotid artery disease who had not had strokes.

The carotid arteries are the two large blood vessels in the neck that supply blood to the brain.

MicroRNAs (miRNAs) are small RNA strands that are involved in a wide range of biological functions, including immune response and inflammation. Their discovery in the late 1990s led to a 2006 Nobel Prize for the investigators who first identified them.

MiRNA 'Signature' Signaled Unstable Plaque

When the Italian research team examined carotid artery plaque samples taken from seven stroke patients and eight patients who had not had strokes, they found clear differences in expression among the stroke and non-stroke samples for five of the 41 miRNAs examined.

When they repeated the testing in a second group of 15 stroke patients and 23 non-stroke patients, all five of the miRNAs were found to be expressed significantly more often in the stroke patients.

The miRNA signature linked to vulnerable plaques was not associated with a higher presence of specific risk factors for stroke, including diabetes, high blood pressure, and smoking. This suggests that metabolic risk does not fully explain the impact of miRNA on plaque, the researchers say.

American Heart Association immediate past president Ralph Sacco, MD, tells WebMD that the research represents an "interesting first step" in the search for a genetic marker for unstable plaque.

Sacco is chairman of the neurology department at the Miller School of Medicine at Florida's University of Miami.

"This was a small study, but the researchers did confirm in two different populations that these microRNAs can distinguish between stable and unstable plaque," he says. "But much more research remains to be done."

Sacco notes that most of the research on unstable plaque has been in the area of artery imaging, in an effort to visually recognize differences associated with plaque stability.

He says much of this research is also promising, and he predicts that a combination approach that includes a patient's risk factors for artery disease along with imaging and possibly genetic markers will lead to better ways to identify patients at risk.

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SOURCES: Cipollone, F. Stroke, published online Aug. 4, 2011.Ralph Sacco, MD, chairman, neurology department, Miller School of Medicine, University of Miami.News release:American Heart Association.News release, Nobel Assembly. ©2011 WebMD, LLC. All Rights Reserved.

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