Cleveland Clinic Researchers Identify Mechanism Behind Platelet Function And Potentially Fatal Blood Clot Formation

Main Category: Cholesterol
Also Included In: Cardiovascular / Cardiology;  Stroke;  Clinical Trials / Drug Trials
Article Date: 28 Aug 2007 - 0:00 PDT

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Researchers at Cleveland Clinic have identified the mechanism that accounts for platelet hyper responsiveness during abnormal blood cholesterol levels, the major risk factor for fatal heart attacks and strokes.

In their work, researchers led by Eugene A. Podrez, M.D., Ph.D., of Cleveland Clinic's Lerner Research Institute, Department of Molecular Cardiology, investigated the mechanisms of how platelets become hyperreactive during hyperlipidemia, a condition in which there are abnormal levels of cholesterol or other lipids in the blood. It has long been recognized that high fat diet and abnormal lipid levels can alter platelet function, increasing chances of creating potentially lethal blood clots causing heart attack and stroke.

"By identifying mechanisms responsible for the hyperactivity of platelets during hyperlipidemia, new therapies may be developed to prevent inappropriate platelet activation and reduce the risk of adverse cardiovascular events," Dr Podrez said.

Low-density lipoprotein (LDL) cholesterol is often called "bad" cholesterol because it can accumulate in blood vessel walls, narrowing vessels and reducing blood supply to vital organs. In addition, platelets become hyperreactive (easily activated) with abnormal cholesterol levels. Excessive platelet activation can lead to blood clot formation and blockage of vital blood vessels during heart attack or stroke.

"Life-threatening cardiovascular events, such as heart attack and stroke, occur when plaque or fatty deposits rupture and trigger the formation of blood clots inside blood vessels," said Stanley Hazen, M.D., Ph.D., Section Head of Preventive Cardiology and Co-Investigator on the study.

Using human clinical studies and mouse models, the researchers found that CD36 on platelets modulates platelet activity in response to oxidant stress and abnormal lipids in the blood. The researchers demonstrated that platelets from humans lacking CD36, a rare genetic disorder, have altered platelet responsiveness. They further demonstrated that the genetic deletion of CD36 could protect mice fed a high fat diet from developing hyperreactive platelets. Prior studies by Maria Febbraio, Ph.D., and Roy Silverstein, M.D., researchers in the Lerner Research Institute's Department of Cell Biology, and Co-Investigators on the study, showed genetic deletion of CD36 protects mice from atherosclerosis, the accumulation of plaque in blood vessels.

In addition to Drs. Febbraio, Hazen, Podrez and Silverstein, the research team also comprised Tatiana Byzova, Ph.D., and Renliang Zhang, M.D., Ph.D., of Lerner Research Institute and Robert Salomon, Ph.D., of Case Western Reserve University.

The researchers' findings appear in "Platelet CD36 Links Hyperlipidemia, Oxidant Stress and Prothrombotic Phenotype," a paper published online on Aug. 26 in the journal Nature Medicine.

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 Case Western Reserve University -- 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 http://www.clevelandclinic.org.

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