Plasma OxLDL

One of the complications associated with type II diabetes is eye disease and several studies have also shown an association of macular degeneration and atherosclerosis (Mullins et al. 2000 Friedman 2000). In that context, it was suggested that PON gene polymorphisms and plasma OxLDL levels may be risk factors for age-related macular degeneration (Ikeda et al. 2001). 

Calvo, D, Gomez-Coronado, D, Lasuncion, MA, and Vega, MA, 1997. CLA-1 is an 85-kD plasma membrane glycoprotein that acts as a high-affinity receptor for both native (HDL, LDL, and VLDL) and modified (OxLDL and AcLDL) lipoproteins. Arterioscler Thromb Vase Biol 17, 2341-2349. 

Associations of several autoimmune diseases with atherosclerosis have been observed and a role for LDL oxidation especially in systemic lupus erythematosus (SLE) has been suggested (Frostegard et al. 2005 Hayem et al. 2001 Svenungsson et al. 2001). OxLDL forms immune complexes with p2GPI, which can be detected in the plasma of patients. OxLDL/p2GPI complexes have been demonstrated in patients with syphilis, infectious endocarditis, diabetes melli-tus, antiphospholipid syndrome and chronic nephritis, indicating that oxidation of LDL and the formation of complexes with p2GPI is not restricted to SLE. It is hypothesized that these autoantibodies accelerate the development of atherosclerosis in autoimmune patients. 

Both circulating OxLDL and MDA-LDL have been measured in plasma by ELISA. Most commonly, the capture antibody is a monoclonal antibody against OxLDL or MDA-LDL and the detection antibody, a polyclonal or monoclonal antibody directed against apo B (El, S12, Tl). Usually, the capture antibody is developed against chemically modified MDA-LDL or OxLDL but antibody has been developed against homogenate of human arteriosclerotic plaque. This antibody reacted with oxidized phosphatidylcholines but not native LDL, or MDA-LDL (S12). 

There is general agreement that there is a relationship between plasma levels of oxidatively modified LDL and arteriosclerosis (HIO) and that its measurement may be a valuable clinical predictor of arteriosclerosis. OxLDL is a complex particle, and monoclonal antibodies react at a single epitope that may not reflect the complexity of the particle thus, it is not surprising that there are some inconsistencies in the exact results from different studies. Not only does this research seem promising in terms of identifying new markers for predicting CAD, but these types of assays are well within the scope of those that fit into the clinical laboratory for widespread use. It seems that continued studies to determine more exact relationships are well warranted. 

Measurement of modified proteins may be an alternative or supplement to measuring products of peroxidation. Direct measurement of OxLDL in plasma appears to be a promising avenue for risk assessment in clinical laboratories. This technique utilizes ELISA that lends itself to automation. Studies indicate that elevated levels of OxLDL correlate with CAD and add predictive value to assessment by conventional lipoprotein lipids (El, H7, HIO, S12). Still, basic and clinical research is needed to determine exactly what is being measured, where it originates, and whether or not it is a cause of arteriosclerosis or only secondarily associated with it. Applied research is needed to determine how best to measure and standardize the assays, and randomized clinical studies are needed to determine the exact diagnostic usefulness. 

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). 

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