The heat that hurts

Inflammation and the development of heart disease

Editor’s Note:  This story, first published in 2004, has been updated.

Harold Olivey
Published: December, 2004

MacRae Linton, M.D., and Sergio Fazio, M.D., Ph.D., surrounded by images of cholesterol-engorged “foam cells,” have found tantalizing molecular and cellular clues supporting a link between inflammation, heart disease and metabolic syndrome.
Photo illustration by Dean Dixon
When it comes to heart disease, fat in the bloodstream is one of the major culprits. Yet as many as 50 percent of people with atherosclerosis—artery blockage that can lead to a heart attack—do not display traditional risk factors such as high cholesterol.

Thanks to recent technological advances, scientists are now able to take a closer look at what stubbornly remains the nation’s leading disease killer. What they are finding may surprise you.

Inflammation, incited by a plethora of infection-fighting and wound-healing blood cells and molecules, seems to play a major role in atherosclerosis. For example, high levels of C-reactive protein (CRP), a circulating marker of inflammation, are associated with an increased risk for heart attack and stroke.

That doesn’t mean a once-a-day anti-inflammatory pill to prevent heart disease is right around the corner. Researchers are hopeful, however, that their pursuit of inflammation may lead to better ways of treating and preventing not only heart disease and other ailments of the Western lifestyle—including type 2 diabetes.

The Vanderbilt connection

Vanderbilt’s contributions to the field of inflammation and heart disease began more than a decade ago, when, as a resident physician, MacRae Linton, M.D., became interested in atherosclerosis. “I would see all these people having bypass surgery, and nobody was thinking about their risk factors,” recalls Linton, now professor of Medicine and Pharmacology at Vanderbilt.

Linton’s interest led him to pursue an endocrinology fellowship at the renowned Gladstone Institute of Cardiovascular Disease at the University of California, San Francisco. There he met Sergio Fazio, M.D., Ph.D., another research fellow who was studying how the body handles cholesterol.

“The real excitement came from understanding the complexity of lipid metabolism,” recalls Fazio, an Italian native whose doctorate is in Molecular Biology. “But when you look at it from the point of view of clinical relevance, what’s important is the damage that lipid metabolism can do to the vessel wall. It was clear that we needed to become vascular biologists.”

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