Cleveland Clinic receives NHLBI grant to identify new pathways linked with cardiovascular diseases

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.