Oxidized low-density lipoprotein (Ox-LDL) has been studied for over 25 years. Numerous pro- and anti-atherogenic properties have been attributed to Ox-LDL. Yet, Ox-LDL has neither been defined nor characterized, as its components and composition change depending on its source, method of preparation, storage, and use. It contains unoxidized and oxidized fatty acid derivatives both in the ester and free forms, their decomposition products, cholesterol and its oxidized products, proteins with oxidized amino acids and cross-links, and polypeptides with varying extents of covalent modification with lipid oxidation products, and many others. It seems to exist in vivo in some form not yet fully characterized. Until its pathophysiological significance, and how it is generated in vivo are determined, the nature of its true identity will be only of classical interest. In this review, its components, their biological actions and methods of preparation will be discussed.

Paraoxonase 1 (PON1) is a hydrolytic enzyme with wide range of substrates, and capability to protect against lipid oxidation. Despite of the large number of compounds that can be hydrolyzed by paraoxonase, the biologically relevant substrates are still not clearly determined. There is a massive in vitro and in vivo data to demonstrate the beneficial effects of PON1 in several atherosclerosis-related processes. The enzyme is primarily expressed in liver; however, it is also localized in other tissues. PON1 attracted significant interest as a protein that is responsible for the most of antioxidant properties of high-density lipoprotein (HDL). Several bioactive molecules such as dietary polyphenols, aspirin and its hydrolysis product salicylate, are known to stimulate PON1 transcription activation in mouse liver and HepG2 cell line. Studies on the activity, function, and genetic makeup have revealed a protective role of PON1. Some striking data were obtained in PON1 gene knockout and PON1 transgenic mouse models and in human studies. The goal of this review is to assess the current understanding of PON1 expression, enzymatic and antioxidant activity, and its atheroprotective effects. Results from in vivo and in vitro basic studies; and from human studies on the association of PON1 with coronary artery disease (CAD) and ischemic stroke will be discussed.

Low-dose aspirin therapy has become a standard in the treatment of cardiovascular diseases. Aspirin has been shown to inhibit atherosclerosis in mouse models. To determine the mechanisms by which aspirin might inhibit atherosclerosis, we incubated HEPG2 cells and rat primary hepatocytes with aspirin or salicylic acid and noted an increase in paraoxonase 1(PON1) activity in the medium, together with an induction of PON1 and apolipoprotein A-I (apoA-I) gene expression. Mice treated with aspirin also showed a 2-fold increase in plasma PON1 activity and a significant induction of both PON1 and apoA