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Paraoxonase (PON1)

Here is an interesting message about paraoxonase from colleague Dan Southern.

“Have you ever heard of paraoxonase? The article below, out of Cleveland Clinic, makes me want to be tested yesterday.” “Cleveland Clinic Researchers Show Strong Relationship Between HDL-Associated Protein And Protection From Heart Disease Risk”

Findings Appear in Special Genetics in Medicine Issue Published by Journal of the American Medical Association on March 19.

Detailed description follows…

Cleveland Clinic Heart and Vascular Institute and Lerner Research Institute investigators are reporting that a protein carried by high-density lipoprotein (HDL), the carrier of so-called “good cholesterol,” plays a significant role in the prevention of heart disease.

In their work, researchers led by Stanley Hazen, MD, PhD, head of the Section of Preventive Cardiology and Rehabilitation at Cleveland Clinic and Faculty in Lerner Research Institute’s Department of Cell Biology, showed that the protein, PON1 (paraoxonase), promotes potent anti-oxidant activity in humans and is strongly linked to protection from heart attack, stroke and death in subjects. They also determined that measurement of PON1 activity serves as an important predictor of increased risk for major adverse cardiac events (MACE), even in subjects not otherwise identified as being at risk.

“In our study, we performed a large, prospective, comprehensive evaluation of PON1, using genetic and biochemical analysis, to see if the tests could predict future risks for heart attack, stroke, death and major adverse cardiac events,” Dr. Hazen said. “Our data shows that both genetic and biochemical measures of PON1 are associated with increased future risk for developing heart attacks, stroke, death and MACE.”

In the study, the measurement of PON1 activity in serum in patients was shown to predict increased risk for adverse cardiac conditions over a three-year period in individuals with no known coronary artery disease and who had just undergone a cardiac catheterization that showed no significant heart disease.

“The ability to predict risk for heart attacks, stroke and death over three years in individuals without a history of heart disease who have just undergone a cardiac catheterization that showed essentially normal results is astounding,” Dr. Hazen said. “It makes low serum PON1 activity levels an incredibly powerful risk predictor for identifying individuals at risk who are not currently deemed as such with current medical screening practices.”

HDL is known to transport cholesterol from artery walls to the liver (Reverse Cholesterol Transport) from where the cholesterol can enter the intestines and ultimately be eliminated from the body. HDL also exhibits alternative athero-protective properties such as helping to prevent inflammation and the generation of harmful oxidants that contribute to artery wall injury and the development of heart disease. Researchers have previously hypothesized that some of the beneficial functions of HDL may be mediated entirely, or in part, by proteins that are carried on HDL like cargo, including PON1.

Until now, researchers’ understanding of the cardio-protective properties linked to PON1 has been predominantly based on animal studies. Prior research has shown that animals in which PON1 has been genetically deleted have accelerated atherosclerosis or accumulation of plaque in the arteries, whereas animals with increased levels of PON1 are protected from developing atherosclerosis.

Dr. Hazen’s study examined the association between PON1 activity measures and heart disease in 1,399 subjects who underwent elective diagnostic coronary angiography between September 2002 and November 2003 at Cleveland Clinic.

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