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Using A Pediatric Perspective to Prevent Heart Disease
New Study by CHORI Scientists Identifies A Novel Gene Associated with Cardiovascular Disease Risk in Women

In a new study just published in the January issue of Arteriosclerosis, Thrombosis and Vascular Biology, CHORI scientists David Iovannisci, PhD and Edward Lammer, MD and their colleagues report for the first time an association between a polymorphism in the leukotriene C4 synthase (LTC4S) gene and increased risk for cardiovascular disease in women.

The study is based on data that is continuing to be gathered through the Muscatine Study, conducted out of the University of Iowa, which was launched in 1970 and is designed to determine at what ages, and how early, one can identify the known risk factors for coronary disease and stroke.

"It's a pediatric perspective on atherosclerosis, which is an adult disease," says Dr. Lammer. "These people have now been tracked for 30 years."

A genetic component has never been added to any analyses before, however, and provides a unique opportunity to investigate genetic predispositions in a population of individuals that do not yet have atherosclerosis.

"Some people do not develop known risk factors for coronary artery disease (like elevated blood pressure) until they are in their 30's or 40's, so when they're younger, you do not know which people on whom to focus preventive interventions," explains Dr. Lammer. "But for genetic risks, you could determine those at any age, especially in childhood."

Whether LTC4S is one of those genes that could be used as a tool to determine risk remains to be seen, however. Researchers like Drs. Lammer and Iovannisci are still exploring the link between atherosclerosis and LTC4S, which, it turns out, is the gene for an enzyme that plays a key role in the inflammatory process.

While cholesterol and dietary fats are well known as heart disease culprits, scientists have begun in the last decade to accumulate significant evidence that the inflammatory process is also very important. Inflammation is involved in healing common nicks that occur in the lining of vascular walls; imperfections in repairing these nicks are probably a significant contributor to coronary artery disease and stroke.

"The way inflammation normally works is that white blood cells are recruited to heal injuries to the vascular wall, which causes the release of signaling molecules that recruit additional white cells as part of the healing process," explains says Dr. Iovannisci.

"However, the LTC4S variant we identified causes increased expression of those signaling molecules, so that the recruitment response to injury is much greater in people who have this variant than people who don't."

As a result, the new study not only identifies a novel genetic risk factor for atherosclerosis in women, but it also confirms the importance of inflammation in the pathogenesis of atherosclerosis.
"What our research is pointing the finger at is that a person's inflammatory response is an important part of that healing process and either environmental or genetic influences over how that healing process occurs predispose you to develop coronary disease and stroke later," says Dr. Lammer.

Dr. Lammer also urges a certain amount of caution, however. "We need more confirmation about the role of inflammation in particular in older adults that already have had strokes or heart attacks to see whether we can show if the gene is a risk factor in that population as well."

Drs. Iovannisci and Lammer are already working on some of those studies and hope to provide a complete survey of the LTC4S gene in the near future. In the mean time, however, their study has brought research one step further in identifying potential tools to determine the genetic risk of heart disease, and in so doing, one step closer to the long term goal of prevention.

"If we can identify those people who eventually progress to illness, before they progress to illness," says Dr. Iovannisci, "then we could in the future intervene much earlier, at a time when therapies are much more likely to be beneficial and actually prevent the disease to begin with."

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Monday, May 16, 2011 11:33 PM

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