HMS FACULTY SYMPOSIUM

Getting to the Molecular Heart of Heart Disease

Even though cardiovascular disease ranks first among deadly pathologies, clinicians still have difficulty predicting who will get the disease and why. At the HMS Faculty Symposium on June 7, HMS alums and others had a chance to hear about the latest research on the causes of cardiovascular disease and how these findings can be moved into the clinic.

Liza Green, HMS Media Services

Robert Gerszten (right) and Guillermo Garcia-Cardena both have brought new technology to bear on fundamental questions about cardiovascular disease.

Michael Gimbrone and Guillermo Garcia-Cardena detailed emerging science about the relationship between blood flow and blood vessel identity in health and disease. Gimbrone, the Elsie T. Friedman professor of pathology at HMS and Brigham and Women’s Hospital, recounted research in his lab showing that the force of blood flow helps determine where atherosclerotic plaques form. His team discovered that different types of fluid force could actually turn genes on and off in the endothelial lining of blood vessels and “with that, came an epiphany, quite frankly, for us as vascular biologists.” Atherosclerotic plaques form in areas with turbulent flow, while areas with smooth flow are protected from plaques. By identifying genes that are switched on in the two regions, his team has shown that understanding tissue mechanics can lead to molecular pathology insights—and point the way to novel therapeutic agents.

Garcia-Cardena, HMS assistant professor of pathology at BWH, spoke about a fundamental question of cardiovascular science: what’s the difference between arteries and veins? His lab has found that different types of blood flow in arteries and veins shape the physical arrangement of endothelial cells and surrounding smooth muscle, triggering different patterns of gene expression. Garcia-Cardena added that the science sheds light on what happens during coronary bypass grafts, in which a piece of vein is inserted into an artery and must adopt the characteristics of the arterial wall.

To demonstrate how new scientific findings can affect the clinic, Paul Ridker began his talk by pointing to a slide that he shows to medical students—a photograph of a severely atherosclerotic artery paired with an image of hands misshapen from arthritis. Research has shown that the two diseases, though very different in nature, “are remarkably similar at a pathophysiological level,” said Ridker, the Eugene Braunwald professor of medicine at BWH. He detailed a string of studies over the past decade showing that C-reactive protein (CRP), a marker of inflammation, may also function as a predictor of heart attack and stroke. He said that CRP or similar inflammatory markers could help clinicians better predict a person’s risk of developing heart disease.

Emergency departments across the country receive five million visits per year for chest pain, yet there are no biomarkers in the blood to determine whether someone is experiencing myocardial ischemia or is in the very earliest stages of a heart attack.

Clinicians still lack tools to rapidly diagnose and treat acute injuries to the heart, said Robert Gerszten. He noted that emergency departments across the country receive five million visits per year for chest pain, yet there are no biomarkers in the blood to determine whether someone is experiencing myocardial ischemia or is in the very earliest stages of a heart attack. Gerszten, HMS associate professor of medicine at Massachusetts General Hospital, is applying the new approach of metabolomics to the problem, which involves characterizing the metabolites in human plasma and the ways they change with disease. To find out what happens to patients during a heart attack, his team has been analyzing metabolites in people undergoing planned myocardial injury as part of a treatment, as well as patients undergoing stress tests. Metabolites are good indicators of acute disease, he said, because their levels change well before any shifts in gene expression. The varying patterns of metabolites might hold biomarkers of an ailing heart or targets for therapeutic manipulation.

—Courtney Humphries

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