The growing importance of PON1 in cardiovascular health: a review

The wide acceptance of the oxidation theory of atherogenesis has prompted attention to antioxidant mechanisms, particularly the prevention of lipid oxidation by high-density lipoprotein-associated proteins like paraoxonase 1 (PON1) enzyme. PON1 is a calcium-dependent enzyme that has interested toxicologists since its discovery as an organophosphate hydrolase. There is a growing interest in the enzyme's importance in cardiovascular health prompted by evidence that it may have a role in lipid metabolism and the development of atherosclerosis via its antioxidant effects. PON1 is capable of hydrolyzing homocysteine thiolactone, a metabolite of homocysteine that can impair protein function leading to endothelial dysfunction and vascular damage. Although this lactonase activity has been suggested to be PON1's native activity, the enzyme's specific physiological role and substrate remain unclear. In this review, we summarize developments in the field of PON1 research relating to cardiovascular health, and highlight those that perhaps warrant further research. J Cardiovasc Med 2012, 13:443-453