Obscure Enzyme May Play Major Role in
Heart Disease

Contact: Martha Molnar martha@ats.org
(212) 307-2580
American Society for Technion, Israel Institute of Technology

NEW YORK, N.Y. and HAIFA, Israel, April 14, 1998 -- A little-known enzyme mayplay a significant role in preventing heart attack. A paper appearing April 15in the prestigious Journal of Clinical Investigation, reports that paraoxonase,an enzyme present in the blood, prevents the oxidation of low-densitylipoprotein or LDL, the "bad cholesterol" that is deposited in blood vessels andleads to coronary heart disease. The paper is by Professor Michael Aviram, abiochemist, head of the Lipid Research Laboratory, Faculty of Medicine at theTechnion-Israel Institute of Technology and at Rambam Medical Center in Haifa,Israel.

"Paraoxonase is located in the blood on the HDL, the 'good' cholesterol,and it can break down oxidized LDL to non-harmful products," explains Aviram,adding that the discovery of this enzyme's activity opens a possible new routeto prevention of heart diseases.

The real function of the enzyme has been something of a mystery since itwas discovered more than 40 years ago. Its previously known function was tobreak down organophosphates, chemicals that are used as insecticides and poisongases. That activity was obviously not the complete story of paraoxonase, ashumans do not normally contain these substances in their blood, Aviram realized.

Since the major focus of his past research has been the study of themechanisms by which oxidized cholesterol and other oxidized lipids accumulate inarterial wall cells, leading to blockage of arteries and formation ofatherosclerotic lesions, he decided to study the effect of the enzyme onoxidized lipids. Researchers had previously found a very strong inverserelationship between the activity of paraoxonase in the blood and the risk ofheart disease. Lower activity is associated with higher risk. The present studyhelps us understand the mechanism behind that relationship.

In experiments with a strain of mice that are vulnerable toatherosclerosis, an inverse relationship between cholesterol oxidation andparaoxonase activity was shown. In addition, an increase in the size of theatherosclerotic lesions in the blood vessels of these mice was found to berelated to the reduction in paraoxonase activity.

The next step, Aviram said, is "to find out how to regulate the activityof paraoxonase and to increase its level in human blood. If we can find means ofchangingt the enzyme activity, we can look for methods of intervention. Thiscould have very strong implications for heart disease therapy."

Aviram has worked for the past decade on the mechanism by which bloodcholesterol quantity (cholesterol levels), as well as blood cholesterol quality(cholesterol oxidation) affects atherosclerosis. He has shown that patientswith a high risk of coronary heart disease have increased LDL oxidation. He hasalso shown that mice and humans given dietary antioxidants, such as red wine orlicorice polyphenols, have reduced oxidation of their LDL and, in parallel inthe mice, reduced atherosclerotic lesion size was demonstrated.

"But dietary antioxidants may not be enough," Dr. Aviram says. "Undercertain conditions, the oxidative stress in the body is so great that itoutpaces the activity of the antioxidants. Thus, the combination of preventingLDL oxidation by antioxidants with the breakdown of oxidized lipids byparaoxonase, may be important in reducing oxidative stress and the resultingatherosclerosis."

The research reported by Aviram was done at the Technion-IsraelInstitute of Technology and at the University of Michigan Medical School, wherehe is a visiting professor working with Dr. Bert N. La Du, a leading authorityon paraoxonase.

The Technion-Israel Institute of Technology is the country's premier scientificand technological center for applied research and education. It commands aworldwide reputation for its pioneering work in communications, electronics,computer science, biotechnology, water-resource management, materialsengineering, aerospace and medicine, among others. The majority of Israel'sengineers are Technion graduates, as are most of the founders and managers ofits high-tech industries. The university's 11,000 students and 700 faculty studyand work in the Technion's 19 faculties and 30 research centers and institutesin Haifa.

The American Technion Society (ATS) is the university's support organization inthe United States. Based in New York City, it is the leading Americanorganization supporting higher education in Israel. The ATS has raised $650million since its inception in 1940, half of that during the last six years.Technion societies are located in 24 countries around the world.

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