Public Release:  Cleveland Clinic researchers receive $5 million grant to discover novel pathways to heart disease

Study builds on research team's prior work linking gut flora to atherosclerosis

Cleveland Clinic

Thursday, July 12, 2012, Cleveland: The National Heart, Lung, and Blood Institute (NHLBI) has awarded a $4.78 million grant to researchers at Cleveland Clinic's Lerner Research Institute to use metabolomics - a new approach that focuses on the small-molecule byproducts of metabolism - for discovery of novel pathways linked to the development of cardiovascular diseases.

"Despite the identification of numerous genetic and clinical risk factors for cardiovascular disease, we can still only explain in a small fraction of patients why that individual develops the disease; this means many novel pathways contributing to the disease still remain unexplored," said Stanley Hazen, M.D., Ph.D., vice chair of the Lerner Research Institute and section head of Preventive Cardiology & Rehabilitation in the Miller Family Heart and Vascular Institute.

Hazen is co-principal investigator on the study with W.H. Wilson Tang, M.D., director of the Cardiomyopathy Program at Cleveland Clinic, and research director of the Section of Heart Failure and Cardiac Transplantation Medicine in the Miller Family Heart and Vascular Institute.

"By using metabolomics approaches, our goal is to better understand at the molecular-level the mechanisms that cause cardiovascular diseases," said Dr. Tang. "Metabolomics is a powerful discovery platform, and can help lead to improved diagnostics and better treatments to prevent development and progression of cardiovascular disease."

Dr. Hazen and his colleagues' prior research in this area has been successful in discovering new and unexpected pathways involved in heart disease. Last year they identified a dietary nutrient found in animal products that is metabolized by gut flora and linked to atherosclerosis, or the hardening or clogging of the arteries. In a study published in Nature, they found that people are not predisposed to cardiovascular disease solely on their genetic make-up, but also based on how the micro-organisms in their digestive tracts metabolize a specific lipid - phosphatidylcholine (also called lecithin). For that discovery, Dr. Hazen and his research team were honored with an inaugural Top 10 Clinical Research Achievement Award from an organization comprised of the nation's most prestigious and acclaimed academic medical centers and other groups.

With the NHLBI grant, Dr. Hazen and his colleagues will extend their research by further analyzing the thousands of metabolites in blood, including many that are formed by gut flora, in order to discover pathways linked to causing heart attacks, strokes, and heart failure. They also propose to manipulate the bacteria in humans, testing whether specific probiotics can play a role in treatment of cardiovascular disease. The research can thus ultimately lead to new treatments, including diets and drugs, for cardiovascular disease as well as improved diagnostics and prevention.

Cleveland Clinic's grant (NHLBI grant number: 1P20HL113452-01) is part of a series awarded by the National Institutes of Health to study the abnormal metabolism of cardiovascular and lung diseases. In addition to Drs. Hazen and Tang, the research team includes co-investigator Zeneng Wang, Ph.D., of Cleveland Clinic; Oliver Fiehn, M.D., of the University of California, Davis; and David Lefer, Ph.D., of Emory University.

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About Cleveland Clinic

Cleveland Clinic is a nonprofit multispecialty academic medical center that integrates clinical and hospital care with research and education. Located in Cleveland, Ohio, it was founded in 1921 by four renowned physicians with a vision of providing outstanding patient care based upon the principles of cooperation, compassion and innovation. Cleveland Clinic has pioneered many medical breakthroughs, including coronary artery bypass surgery and the first face transplant in the United States. U.S.News & World Report consistently names Cleveland Clinic as one of the nation's best hospitals in its annual "America's Best Hospitals" survey. About 2,800 full-time salaried physicians and researchers and 11,000 nurses represent 120 medical specialties and subspecialties. Cleveland Clinic Health System includes a main campus near downtown Cleveland, eight community hospitals and 18 Family Health Centers in Northeast Ohio, Cleveland Clinic Florida, the Lou Ruvo Center for Brain Health in Las Vegas, Cleveland Clinic Canada, and opening in 2013, Cleveland Clinic Abu Dhabi. In 2010, there were 4 million visits throughout the Cleveland Clinic health system and 167,000 hospital admissions. Patients came for treatment from every state and from more than 100 countries. Visit us at www.clevelandclinic.org. Follow us at www.twitter.com/ClevelandClinic.

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