Paraoxonase 1 interactions with atherosclerotic lesions and arterial macrophages protect against foam cell formation and atherosclerosis development

Abstract

Paraoxonase (PON)1 is a HDL-associated enzyme with esterase (lipolactonase)-and peroxidase-like activities that exhibits antiatherogenic properties. PON1 deficiency in mice was shown to be associated with enhanced atherosclerosis development, whereas the overexpression of human PON1 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. PON1 interacts with the atherosclerotic lesion and with macrophages to attenuate their atherogenic properties, whereas the oxidized lesion inactivates PON1. It is of interest that, similarly to HDL-associated PON1 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.

Keywords:

• atherosclerosis
• carotid lesion
• foam cell
• HDL
• lysophosphatidylcholine
• macrophage
• oxidative stress
• paraoxonase