Arteriosclerosis, Thrombosis, and Vascular Biology. 2001;21:473-480
© 2001 American Heart Association, Inc.
Brief Review |
Paraoxonase and Atherosclerosis
From the University of Manchester Department of Medicine, Manchester Royal Infirmary, Manchester, England.
Correspondence to Prof P.N. Durrington, University of Manchester Department of Medicine, Manchester Royal Infirmary, Oxford Road, Manchester M13 9WL, England. E-mail pdurrington{at}hq.cmht.nwest.nhs.uk
Abstract—There is considerable evidence that the antioxidant activity of high density lipoprotein (HDL) is largely due to the paraoxonase-1 (PON1) located on it. Experiments with transgenic PON1 knockout mice indicate the potential for PON1 to protect against atherogenesis. This protective effect of HDL against low density lipoprotein (LDL) lipid peroxidation is maintained longer than is the protective effect of antioxidant vitamins and could thus be more important. There is evidence that the genetic polymorphisms of PON1 least able to protect LDL against lipid peroxidation are overrepresented in coronary heart disease, particularly in association with diabetes. However, these polymorphisms explain only part of the variation in serum PON1 activity; thus, a more critical test of the hypothesis is likely to be whether low serum PON1 activity is associated with coronary heart disease. Preliminary case-control evidence suggests that this is indeed the case and, thus, that the quest for dietary and pharmacological means of modifying serum PON1 activity may allow the oxidant model of atherosclerosis to be tested in clinical trials.
Key Words: paraoxonase • lipid peroxidation • high density lipoproteins
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