Researchers at Cleveland Clinic Identify Site of 'Dysfunction' in HDL, Carrier of Good Cholesterol

Findings Appear Online on Aug. 5 in Nature Journal

CLEVELAND, August 07, 2007 /PRNewswire/ -- Researchers at Cleveland Clinic have identified the region within high density lipoprotein (HDL), the major carrier of "good" cholesterol, that can become dysfunctional within the artery wall, inhibiting the body's ability to fight cholesterol buildup.

The work of the researchers led by Stanley Hazen, M.D., Ph.D., Head of the Section of Preventive Cardiology and Rehabilitation at Cleveland Clinic appears online Aug. 5 in the journal Nature Structural & Molecular Biology in a paper entitled "The Refined Structure of Nascent HDL Reveals a Key Functional Domain for Particle Maturation and Dysfunction." It builds upon the researchers' previous work which determined that not all HDL helps protect arteries from becoming clogged with fatty deposits.

The findings are important because raising HDL levels represents a major target for new treatment strategies of atherosclerosis, the accumulation of harmful plaque in the arteries, by the pharmaceutical industry. Yet it appears that the function as well as the level of the HDL is important. This may also help explain research earlier this year which found that despite raising the level of HDL (good) cholesterol, the drug torcetrapib did not slow the progression of artery disease.

"In this study we describe a refined molecular model of a nascent HDL molecule that is dramatically improved upon its predecessors," Dr. Hazen said. "With our enhanced detail of the HDL molecule structure we are better able to understand the location and mechanics of dysfunction in HDL."

HDL becomes dysfunctional when a specific region on HDL is modified by myeloperoxidase (MPO), an enzyme present in white blood cells and found in atherosclerotic plaque. This inhibits HDL's ability to mature and effectively carry cholesterol cargo from cells of the artery wall. In their paper, the researchers describe the HDL as having a "solar flare" structure.

Zhiping Wu, Ph.D., a research fellow at Cleveland Clinic is the paper's first author. Valentin Gogonea, Ph.D., an Associate Professor in the Department of Chemistry at collaborated in the research.

About Cleveland Clinic's Lerner Research Institute

The Lerner Research Institute is home to Cleveland Clinic's laboratory-based and translational biomedical research. Its mission is to understand the causes of human diseases and to develop new treatments and cures. The Lerner Research Institute's total annual research expenditures exceed $120 million from Federal agencies, non-Federal societies and associations, endowment funds and the Cleveland Clinic. More than 1,100 people (including about 160 investigators, 350 junior faculty and postdoctoral fellows, and 120 graduate students) work in research programs focusing on cardiovascular, cancer, neurologic, musculoskeletal, allergic and immunologic, eye, metabolic, and infectious disease. The Institute also is an integral part of the Cleveland Clinic Lerner College of Medicine of - training the next generation of physician-scientists.

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. Cleveland Clinic 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. Approximately 1,800 full-time salaried physicians and researchers at Cleveland Clinic and Cleveland Clinic Florida represent more than 100 medical specialties and subspecialties. In 2006, there were 3.1 million outpatient visits to Cleveland Clinic. Patients came for treatment from every state and from more than 80 countries. There were more than 53,000 hospital admissions to Cleveland Clinic in 2006. Cleveland Clinic's Web site address is www.clevelandclinic.org.

Cleveland Clinic

CONTACT: Erinne Dyer, +1-216-444-8168, or Raquel Santiago,+1-216-444-4235, , both of Cleveland Clinic dyere@ccf.org santiar@ccf.org

Web site: http://www.clevelandclinic.org/

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Posted: August 2007

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