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New discoveries from Harvard and Baylor get to the heart of cardiovascular disease

June 19, 2008

Even if you eat right and exercise regularly, chances are high that you'll still die of a heart attack or stroke. But thanks to new findings by researchers from Harvard and Baylor, the odds may finally shift in your favor. Two unrelated studies recently published online in The FASEB Journal (http://www.fasebj.org) describe findings on atherosclerosis that have the potential to save millions of lives.

Both studies involved experiments in mice, but cover biological processes present in humans. In the first, scientists from Harvard explain how the absence of a single protein, called "ROCK1," profoundly reduces inflammation in the walls of blood vessels provoked by fatty deposits (atherosclerosis). In this study, scientists found that ROCK1 is necessary for immune cells, called macrophages, to "clean up" vascular walls when they come into contact with fatty deposits. Inflammation is a normal byproduct of the clean-up process and, when it goes unchecked, leads to clogging and hardening of the arteries. When ROCK1 is absent, macrophages no longer contributed to these fatty deposits and mice showed significantly less inflammation and atherosclerosis. This discovery could lead to new treatments, such as ROCK1 inhibitors, that could dampen the inflammatory response to fatty deposits and slow the progression of atherosclerosis, and in so doing, reduce the incidence of heart attacks and strokes.

According to James Liao, MD, Director of Vascular Medicine Research, Brigham and Women's Hospital, Harvard Medical School, and one of the report's co-authors, "the ultimate goal of the research is to prevent or slow atherosclerosis, and these findings provide a new target to do this."

While the first study works to prevent inflammation by keeping cells of the immune system at bay, the second report focuses on the body's ability (or inability) to "cool down" inflammation after this clean-up machinery kicks into high gear. Separate researchers from Harvard, Brigham and Women's Hospital and Baylor looked at how we prevent inflammation from running amok. The scientists identified lipid mediators that the body uses to resolve inflammation once it has started. By targeting these lipid mediators and the mechanisms used to make them, scientists should be able to develop drugs that significantly reduce the inflammation that underlies much of atherosclerosis.

"The specific chemical mediators that naturally cool down the inflammatory process identified in this study represent a new drug target for anti-atherosclerosis therapy," said Aksam Merched, PhD, Assistant Professor at Baylor College of Medicine and the first author of the study. "It's also noteworthy that aspirin stimulates the body to produce one class of these chemicals."

"Even if we delay the process by exercise and rabbit food, sooner or later our blood vessels rot," said Gerald Weissmann, MD, Editor-in-Chief of The FASEB Journal. "Now that we appreciate that atherosclerosis is inflammation gone awry, we can attack its root causes. Studies like these take us closer to delaying the inevitable, and help us understand the factors that provoke heart attacks and strokes."

And as the first study aims to prevent atherosclerosis before the immune system kicks into gear and the second aims to prevent it after the immune system is activated, a third study appearing on the cover of the June 2008 print issue of The FASEB Journal (www.fasebj.org) discusses a new approach toward repairing the damage using artificial grafts that may heal into the natural arteries and blood vessels as time goes on. Find out more about this by visiting The FASEB Journal online at www.fasebj.org and clicking "Press Room."

According to the U.S. Centers for Disease Control and Prevention, heart disease is the number one killer of Americans and a major cause of disability. About 29 percent of all U.S. deaths are from heart disease (approximately 700,000 a year). Stroke is the leading cause of disability in the United States and the third leading cause of death. By reducing the incidence of atherosclerosis, the risk of fatal heart attacks or strokes would decrease significantly.

Federation of American Societies for Experimental Biology