The Role of Oxidized Low-Density Lipoproteins in the Pathogenesis of Atherosclerosis

Abstract

Hypercholesterolemia is a major risk for atherogenesis. Recent evidence suggests that oxidative modification of the major cholesterol-carrying lipoprotein, low-density lipoprotein (LDL), renders it more atherogenic. Not only does oxidized LDL (Ox-LDL) have enhanced uptake by macrophages, which contributes directly to foam cell formation, it may also adversely affect many other aspects of arterial wall metabolism and thus contribute further to the atherogenic process. Inhibition of the oxidation of LDL may be another approach to inhibiting atherogenesis, additive to or even synergistic with lowering of plasma LDL levels.

Caffeic Acid Protects Hydrogen Peroxide Induced Cell Damage in WI-38 Human Lung Fibroblast Cells

“…ROS are associated with tissue damage and are the contributing factors for inflammation, aging, cancer, arteriosclerosis, hypertension and diabetes. [15][16][17][18][19][20][21] The cells have developed a variety of antioxidant defense mechanisms against ROS. Enzymatic defense mechanisms involve superoxide dismutase, which catalyzes dismutation of superoxide anion to hydrogen peroxide, catalase, which converts hydrogen peroxide into molecular oxygen and water, and glutathione peroxidase, which destroys toxic peroxides.…”

Protein Adducts of Iso[4]levuglandin E2, a Product of the Isoprostane Pathway, in Oxidized Low Density Lipoprotein

“…Oxidative modification of low density lipoprotein (LDL) 1 is considered a key step in the etiology of atherosclerosis (1,2).…”

Oxidation of Low Density Lipoproteins Greatly Enhances Their Association with Lipoprotein Lipase Anchored to Endothelial Cell Matrix

“…Low density lipoprotein oxidation is believed to be an early event in the initiation and progression of atherosclerosis (1)(2)(3). The oxidation of LDL 1 confers many biological properties on the molecule that render the lipoprotein more atherogenic (4 -6).…”

“…Some of these effects may result from the activation of transcription factors such as NF-B (21). OxLDL is also avidly scavenged by macrophages (22)(23)(24) and leads to macrophage-derived foam cell formation (3,22). The process of LDL oxidation is not very well understood, but it appears to occur within the artery wall, facilitated by cellular lipoxygenase-dependent mechanisms or by nonenzymatic pathways.…”

“…Due to the oxidative attack, apoB also undergoes cleavage, which exposes neoepitopes on the protein (28). Although most of the biological effects of OxLDL are thought to result from oxidized lipid products, the increased scavenger receptor uptake of OxLDL is mediated by changes in surface protein charge (3). Another important step in the process of atherogenesis is believed to be the trapping of LDL within the subendothelial space.…”