Cleveland Clinic researchers ask why ‘good’ cholesterol goes bad

Cleveland Clinic researchers have won $11.7 million from the National Institutes of Health (NIH) to find out why “good” cholesterol sometimes goes bad, and then to harness their discoveries as new diagnostic tests or therapies for heart disease.

Dr. Stanley Hazen, section head of Preventive Cardiology at Cleveland Clinic’s Miller Heart & Vascular Institute and a staff member in the Department of Cell Biology of its Lerner Research Institute, is the principal investigator on the grant.

Hazen, discoverer of a heart inflammation biomarker, will lead three projects under the latest grant to develop a comprehensive understanding of high-density lipoprotein (HDL) cholesterol and its relationship to atherosclerotic heart disease. He already has landed at least $25 million in grants for heart disease research this year.

Hazen also is a driving force behind a recently struck research deal with Esperion Therapeutics Inc. in Plymouth, Minnesota, to develop good cholesterol therapies to fight cardiovascular disease.

“HDL is typically a protective particle that carries ‘good’ cholesterol,” Hazen said in a Clinic release. “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.”

Plaque that builds up in artery walls can cause heart attacks or strokes.

“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,” Hazen said.

Hazen will lead Project 1 under the latest grant to figure out how and where HDL becomes “dysfunctional” in atherosclerosis. The project also will develop and validate a test for dysfunctional HDL “as a new and powerful diagnostic tool for heart disease risk,” the Clinic said in its release.

Jonathan Smith, a staff member in the Lerner Research Institute’s Cell Biology Department, will lead Project 2, which will try to understand how HDL is made and test engineered forms of HDL as therapies for atherosclerosis.

Finally, Dr. Ed Fisher will lead Project 3, which will seek to understand the molecular mechanisms that cause plaque to regress. Fisher is director of New York University Medical Center’s Vascular Biology and Disease Program.

Hazen’s heart inflammation biomarker — myeloperoxidase — has been commercialized as a test called CardioMPO done by Cleveland Clinic spinoff company Cleveland HeartLab. Hazen is Cleveland HeartLab’s chief scientific officer.

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