Paraoxonase 1 activities, regulation, and interactions with atherosclerotic lesion

Improving serum levels of HDL and its subfractions, as well as, oxidative/inflammatory properties has become a fundamental aim in today's atherosclerosis research. Efforts to reach this goal are paralleled by achievements in drug development toward decreasing serum LDL levels and oxidative status.

Paraoxonase1 (PON1) is an HDL-associated enzyme that is deemed responsible for many of the HDL's antiatherogenic and cardioprotective characteristics. PON1 is highly sensitive to variations in its milieu, and endogenous compounds (fatty acids, phospholipids), nutritional ingredients (flavonoids and other antioxidants), and environmental elements (reactive nitrogen and oxygen species, metals, surfactants), significantly affect the enzyme's activities. PON1 was shown to be responsible for some of the HDL antiatherogenic characteristics such as HDL-mediated cholesterol efflux from macrophages, and the inhibition of LDL oxidation.

The present review summarizes the recent literature related to various elements in PON1's milieu that regulate its activities, with an emphasis on its interrelation with components of the human carotid atherosclerotic lesion (plaque) which are in constant contact with circulating HDL-associated PON1.