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Press Release:
      American Society for Technion, Israel Institute of Technology

Lowered Levels of Enzyme Paraoxonase
ay Play Major Role in
      Increasing Risk of Heart Disease

NEW YORK, N.Y. and HAIFA, Israel, April 14, 1998 -- A little-known
enzyme may play a significant role in preventing heart attack.

A paper appearing April 15 in the prestigious Journal of Clinical
, reports that paraoxonase, an enzyme present in the
blood, prevents the oxidation of low-density lipoprotein or LDL,
the "bad cholesterol" that is deposited in blood vessels and leads
to coronary heart disease.

The paper is by Professor Michael Aviram, a biochemist, head of the
Lipid Research Laboratory, Faculty of Medicine at the Technion-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 route to prevention of heart diseases.

The real function of the enzyme has been something of a mystery
since it was discovered more than 40 years ago.

Its previously known function was to break down organophosphates,
chemicals that are used as insecticides and poison gases.
That activity
was obviously not the complete story of paraoxonase, as humans do
not normally contain these substances [organophosphates] in their
, Aviram realized.

Since the major focus of his past research has been the study of the
mechanisms by which oxidized cholesterol and other oxidized lipids
accumulate in arterial wall cells, leading to blockage of arteries and
formation of atherosclerotic lesions, he decided to study the effect
of the enzyme on oxidized lipids.

Researchers had previously found a very strong inverse relationship
between the activity of paraoxonase in the blood and the risk of heart

Lower activity
[of paraoxonase in the blood] is associated with
higher risk [of heart disease]

The present study helps us understand the mechanism behind that

In experiments with a strain of mice that are vulnerable to atherosclerosis,
an inverse relationship between cholesterol oxidation and paraoxonase
activity was shown. In addition, an increase in the size of the
atherosclerotic lesions in the blood vessels of these mice was
found to be related to the reduction in paraoxonase activity.

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

Aviram has worked for the past decade on the mechanism by which
blood cholesterol quantity (cholesterol levels), as well as blood cholesterol
quality (cholesterol oxidation) affects atherosclerosis. He has shown
that patients with a high risk of coronary heart disease have increased
LDL oxidation.

He has also shown that mice and humans given dietary antioxidants,
such as red wine or licorice polyphenols, have reduced oxidation of
their LDL and, in parallel in the mice, reduced atherosclerotic lesion
size was demonstrated.

"But dietary antioxidants may not be enough," Dr. Aviram says. "Under
certain conditions, the oxidative stress in the body is so great that it
outpaces the activity of the antioxidants.

Thus, the combination of preventing LDL oxidation by antioxidants
with the breakdown of oxidized lipids by paraoxonase, may be
important in reducing oxidative stress and the resulting atherosclerosis."

The research reported by Aviram was done at the Technion-Israel Institute
of Technology and at the University of Michigan Medical School, where he
is a visiting professor working with Dr. Bert N. La Du, a leading
authority on paraoxonase.


The Technion-Israel Institute of Technology is the country's premier
scientific and technological center for applied research and education.
It commands a worldwide reputation for its pioneering work in
communications, electronics, computer science, biotechnology,
water-resource management, materials engineering, aerospace and
medicine, among others.

The majority of Israel's engineers are Technion graduates, as are
most of the founders and managers of its high-tech industries.
The university's 11,000 students and 700 faculty study and work
in the Technion's 19 faculties and 30 research centers and institutes
in Haifa.

The American Technion Society (ATS) is the university's support
organization in the United States. Based in New York City, it is the
leading American organization supporting higher education in Israel.

The ATS has raised $650 million since its inception in 1940, half of that
during the last six years. Technion societies are located in 24 countries
around the world.


Contact: Martha Molnar
(212) 307-2580

 American Society for Technion, Israel Institute of Technology


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