Variation in paraoxonase-1 activity and atherosclerosis.
OBJECTIVE
Paraoxonase-1 (PON1) is an HDL-associated protein of 354 amino acids with a molecular mass of 43 000 Da. It is synthesized in the liver, and in serum it is almost exclusively associated with HDL. PON1 has been reported to be an important contributor to the antioxidant and anti-inflammatory activities of HDL. PON1 impedes oxidative modification of LDL. PON1 serum activity is related to systemic lipid peroxidation stress and prospective cardiovascular risk. In this review, we discuss the relationship between PON1 activity and atherosclerotic diseases and various factors modulating PON1 activity including genes, age, lifestyle factors and medical conditions. Finally, evidence that pharmacological agents may affect PON1 activity is summarized.


RESULTS
There is increasing evidence from both animal and human studies linking low PON1 activity to an increased likelihood of cardiovascular diseases. Two prospective studies reported a significantly lower incidence of major cardiovascular events in participants with the highest systemic PON1 activity, compared with those with the lowest activity.


CONCLUSIONS
PON1 is a potentially antiatherogenic HDL-associated enzyme that protects LDL from oxidative modification. Enhancing PON1 activity could be an important target for future pharmacological agents aimed at decreasing cardiovascular risk.
Soran
Handrean
H
University Department of Medicine, Central Manchester and Manchester Children's University Hospitals Foundation Trust, Manchester, UK.
Younis
Nahla N
NN
Charlton-Menys
Valentine
V
Durrington
Paul
P
D000818:Animals; D043303:Aryldialkylphosphatase / Q000378:metabolism*; D050197:Atherosclerosis / Q000201:enzymology*; D002318:Cardiovascular Diseases / Q000201:enzymology; D005260:Female; D006801:Humans; D008075:Lipoproteins, HDL / Q000378:metabolism; D008297:Male
D008075:Lipoproteins, HDL; D043303:Aryldialkylphosphatase