Paraoxonase I interactions with atherosclerotic lesions and arterial macrophages protect against foam cell formation and atherosclerosis development

Paraoxonase (PON)I is a HDL-associated enzyme with esterase (lipolactonase)- and peroxidase-like activities that exhibits antiatherogenic properties. PON I deficiency in mice was shown to be associated with enhanced atherosclerosis development, whereas the overexpression of human PON I resulted in a significant reduction in atherosclerotic lesion size. Human atherosclerotic lesions contain macrophages and a variety of oxidized lipids, which can facilitate further lesion progression and arterial macrophage oxidation. PON I interacts with the atherosclerotic lesion and with macrophages to attenuate their atherogenic properties, whereas the oxidized lesion inactivates PON I. It is of interest that, similarly to HDL-associated PON I antioxidant properties, PON2 (which is not present in the circulation) possesses similar antioxidant/antiatherogenic characteristics towards arterial macrophage foam cells, the hallmark of early atherogenesis.