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Cleveland Clinic Wins $11 6 Millon NIH Grant to Study Role of HDL in Heart Disease

Research to Study Why “Good” Cholesterol Goes Bad

9/29/10

Researchers in Cleveland Clinic’s Lerner Research Institute have been awarded a $11.65 million grant by the National Institutes of Health to study the role of HDL in heart disease, why this “good” cholesterol sometimes goes bad, and how to possibly harness its plaque-fighting powers for new cholesterol-lowering therapies.

Stanley Hazen, MD, PhD, Section Head of Preventive Cardiology at Cleveland Clinic’s Miller Heart & Vascular Institute and a staff member in the Department of Cell Biology of LRI, is the principal investigator, leading three projects that collectively focus on developing a comprehensive structural, functional, mechanistic and clinical understanding of HDL biology and its relationship to atherosclerotic heart disease.

Atherosclerosis – a common cause of heart attack and stroke – is the build-up of plaque inside artery walls. This plaque can grow large enough to restrict blood flow or may rupture, leading to blood clots that block blood flow and cause a heart attack.

“HDL is typically a protective particle that carries “good” cholesterol. It is considered “good” because it normally helps prevent development of plaque; however, it can become dysfunctional within the vessel wall and lose its beneficial functions. This is why a high HDL cholesterol level is not always protective,” said Stanley Hazen, MD, PhD. “Our goal is to discover the biologic mechanisms that render HDL dysfunctional, and to harness this information for both improved diagnostic tests, and new therapeutic interventions.”

Project 1, led by Hazen, focuses on understanding how HDL – high-density lipoprotein – is rendered “dysfunctional” in atherosclerosis. The project will define how and where HDL becomes modified in the artery wall, inhibiting its function. It will also develop and validate clinical studies of a “dysfunctional HDL” test as a new and powerful diagnostic tool for heart disease risk.

Project 2, led by Jonathan Smith, PhD, a staff member in LRI’s Cell Biology Department, focuses on understanding how HDL is made. The project will also test novel engineered “oxidant resistant” forms of HDL as therapeutics for atherosclerosis.

Project 3, led by Ed Fisher, MD, PhD, Director of New York University Medical Center’s Vascular Biology and Disease Program, focuses on understanding the molecular mechanisms responsible for atherosclerotic plaque regression.

The inter-related projects of the research program may lead to new diagnostic and therapeutic approaches toward cardiovascular risk assessment and therapy.

About Cleveland Clinic

Cleveland Clinic, located in Cleveland, Ohio, is a not-for-profit multispecialty academic medical center that integrates clinical and hospital care with research and education. 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. 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 2,100 full-time salaried physicians and researchers and 11,000 nurses represent 120 medical specialties and subspecialties. In addition to its main campus, Cleveland Clinic operates nine community hospitals and 15 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 2012, Cleveland Clinic Abu Dhabi. In 2009, there were more than 4.6 million visits throughout the Cleveland Clinic health system and 170,000 hospital admissions. Patients came for treatment from every state and from more than 100 countries.

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