Role of Oxidized Lipids in Atherosclerosis

The role of oxidized lipids in cardiovascular diseases (CVD) has been investigated over the last three decades extensively. A number of studies have been carried out on the mechanisms, and pathways leading to the arterial atherosclerosis. These studies originated from the oxidation hypothesis of the atherosclerosis which was originally proposed more than 25 years ago (Steinberg et al., 1989), and since then experiments were performed by many investigators to further examine and explore the contribution of oxidation and oxidized lipids to cardiovascular diseases. Oxidized fatty acids in the ester and free forms, their decomposition products, cholesterol and its oxidized products, proteins with oxidized amino acid residues and cross-links, and polypeptides with varying extents of covalent modification with lipid oxidation products, and many others substances derived from oxidation have been the subject of detailed studies by many investigators. These products originated in vivo from oxidized lipoproteins and lipid membranes were linked to initiation and propagation of atherosclerosis (Zhang & Salomon, 2005; Mitra et al., 2011; Hulsmans et al., 2010). The effect of dietary oxidized fat as a contributor to the oxidative stress was also investigated by several groups including our group (Catapano et al., 2000; Drüeke et al., 2001; Garelnabi et al., 2008; Mitra et al., 2011). While there is a consensus in understanding of initial oxidative steps in the generation of early fatty streak lesions as well as the role of products of peroxidized lipid decomposition such as aldehydes in atherosclerosis, the role of further oxidation into neutral carboxylic acids is still obscure. In this chapter we will review the background of the oxidation theory of lipoproteins and the current state of the knowledge. We will review and summarizes data leading to the current understanding of the role of oxidized lipids in atherosclerosis and some pathways involved in this process. We will also discuss recent studies that elucidate factors leading to oxidative stress including chemical, physical and biological factors. In addition, we will explain the current knowledge of the use of antioxidants; and explain their benefits if any to inhibit oxidation of LDL. This part will discuss in brief some selected clinical data.