Paraoxonases role in the prevention of cardiovascular diseases

Increased oxidative stress is a characteristic of patients with high risk for atherosclerosis development (hypercholesterolemic, hypertensive, diabetic), and the above phenomenon was shown to be associated with attenuated antioxidative status. The increased oxidative stress in atherosclerotic patients is present in their blood, as well as in their arterial wall cells, including macrophages, the hallmark of foam cells formation during early atherogenesis. Serum high density lipoprotein (HDL)-associated. paraoxonase 1 (PON1) reduces oxidative stress in lipoproteins, in macrophages, and in the atherosclerotic lesion, whereas paraoxonase 2 (PON2, which is present in tissues, but not in serum) acts as an antioxidant at the cellular and not humoral level. Both PON1 and PON2 protect against atherosclerosis. development, and this. phenomenon could be related to-their antioxidative properties. The use of nutritional antioxidants such, as vitamin E, carotenoids (lycopene and beta-carotene), and mainly polyphenols (such as those present in red wine, licorice root ethanolic extract, or in pomegranate) by atherosclerotic animals and also by cardiovascular patients, leads to a reduction in oxidative stress. and to the attenuation,of atherosclerosis development. These latter phenomena could be related to the nutritional antioxidants-induced increase in. HDL PON1 activity (effects on gene expression, on preventing enzyme inactivation, and on increasing PON1 stability through its binding to HDL), as well as an increase in. macrophage PON2.. activation (at the gene expression level). (C) 2009 International Union of Biochemistry and Molecular Biology, Inc. Volume 35, Number 1, January/February 2009, Pages 98-104. E-mail: aviram@tx.technion.ac.il