Oxidized low-density lipoprotein oxLDL

Shatrov VA, Sumbayev W, Zhou J, Brtine B (2003) Oxidized low-density lipoprotein (oxLDL) triggers hypoxia-inducible factor-lalpha (HIF-lalpha) accumulation via redox-dependent mechanisms. Blood 101(12) 4847-9... 

Atherosclerosis is a chronic inflammation of the arterial vessel wall resulting in plaque formation that eventually may cause cardiovascular events, such as myocardial infarction or cerebral vascular accidents. The presence of autoimmune components in atherosclerosis is well established. Autoantibodies to heat-shock proteins and oxidized low-density lipoproteins (oxLDL) are prevalent in the circulation of patients with atherosclerosis, but the role of these autoantibodies is debated. While anti-oxLDL IgG antibodies may facilitate uptake of oxLDL by foam cells in the lesions, natural IgM antibodies directed to oxLDL may even protect from atherosclerosis. Atherosclerotic plaques also contain some T cells that are considered to be autoreactive, although the respective autoantigens have not yet been identified. These T cells are probably not involved in the plaque formation as such, but they may cause plaque instability, rupture, and subsequent clinical events. 

Although modifications of ion channels could contribute to the late stages of cardiovascular disease, formation of IsoK/LG adducts may also play a role early in atherosclerosis. Atherosclerosis is initiated when macrophages take up oxidized low density lipoprotein (oxLDL) via scavenger receptors such as SR-A and CD36 to form foam cells. In vitro oxidation of LDL results in the formation of IsoK adducts on the particle (Brame et ah, 1999 Salomon et al., 1997a ... 

FIGURE 14.2 Sources of OxPL and receptors on macrophages. OxPC on the surface of apoptotic cells and from the lipid- and protein-phase of oxidized low-density lipoprotein (OxLDL) are recognized by macrophages via membrane-bound pattern recognition receptors (PRRs). 

In this connection, the type and concentration of oxysterols that are actually detectable in oxidized low-density lipoproteins (oxLDL) and, above all, those detectable in atherosclerotic plaques, must first be considered. 

There is considerable evidence that inflammatory response induced by oxidized low-density lipoprotein (oxLDL) contribute to the development of atherosclerosis. OxLDL or their metabolites have been found in atherosclerotic lesions in both human and animal models (i). OxLDLs have been shown to stimulate endothelial cells to express several proteins that contribute to atherosclerosis, including monocyte chemotactic protein-1 (MCP-1),... 

Ab, Antibody BBB, Blood Brain Barrier CNS, Central Nervous System HIV, Human Immunodeficiency Virus HSA, Human Serum Albumin IGF, Insulin Growth Factor I/R, Ischaemia/Reperfusion MW, Molecular Weight OxLDL, Oxidized Low Density Lipoprotein -R, -receptor sCD4, soluble CD4 VEGF, Vascular Endothelial Growth Factor. 

FIGURE 15.3 Endothelial changes dne to minimally modified/oxidized low-density lipoproteins (mm/oxLDL) are more likely induced by micelles that accumulate in the sub-intimal space of arterial vessels. 

Figure 3 Possible involvement of reactive oxygen species (ROS) in ageing and chronic degenerative disease. OxLDL, oxidized low density lipoprotein.

Fig. 2.1 Sequence of events in atherogenesis and role of low-density lipoprotein. Native LDL, in the subendothelial space, undergoes progressive oxidation (mmLDL) and activates the expression of MCP-1 and M-CSF in the endothelium (EC). MCP-1 and M-CSF promote the entry and maturation of monocytes to macrophages, which further oxidise LDL (oxLDL). Ox-LDL is specifically recognised by the scavenger receptor of macrophages and, once internalised, formation of foam cells occurs. Both mmLDL and oxLDL induce endothelial dysfunction, associated with changes of the adhesiveness to leukoc)des or platelets and to wall permeability.

Gordiyenko, N, Campos, M, Lee, JW, Fariss, RN, Sztein, J, and Rodriguez, IR, 2004. RPE cells internalize low-density lipoprotein (LDL) and oxidized LDL (oxLDL) in large quantities in vitro and in vivo. Invest Ophthalmol Vis Sci 45, 2822-2829. 

Figure 6.4 The role of chemokines in the recruitment of immune cells in atheroscelortic plaques. Low-density lipoprotein (LDL) diffuses from the blood into the innermost layer of the artery, where LDL particles can associate with proteoglycans of the extracellular matrix. The LDL of the extracellular pool is modified by enzymes and oxygen radicals to form molecules such as oxidized LDL (oxLDL). Biologically...

Elevation of plasma cholesterol, particularly low-density lipoprotein cholesterol (LDL-C), is positively correlated with coronary heart disease (CHD), a major vascular disease predominantly causing by atherosclerosis (1,2). Recent studies have indicated that LDL oxidation, endothelial dysfunction, and inflammation play important roles in the molecular pathogenesis of atherosclerosis (3). Oxidized LDL (OxLDL) appears in the circulation and tends to infiltrate into the aortic endothelium (4). Antioxidants, which inhibit LDL oxidative modification, may reduce early atherogenesis and slow down the disease progression to an advanced stage (5). 

---