Lipid Peroxidation and the Oxidative Modification of LDL

Lipid peroxidation is a radical-mediated chain reaction resulting in the degradation of polyunsaturated fatty acids (PUFAs) that contain more than two covalent carbon-carbon double bonds (reviewed by Esterbauer et al., 1992). One of the major carriers of plasma lipids is LDL, a spherical molecule with a molecular weight of 2.5x10 . A single LDL particle contains 1300 PUFA molecules (2700 total fatty-acid molecules) and is 

In contrast to MDA and hydroxynonenai, other aldehyde products of lipid peroxidation are hydrophobic and remain closely associated with LDL to accumulate to mil-limolar concentrations. Aldehydes at these elevated levels react with the protein portion of the LDL molecule, apolipoprotein B (apoB). Accumulated aldehydes bind the free amino groups from lysine residues in addition to other functional groups (-OH, -SH) on the apoB polypeptide. Consequently, the protein takes on a net negative charge and complete structural rearrangement results in the formation of ox-LDL. ox-LDL is no longer recognized by the LDL receptor, and has several pro-inflammatory properties (discussed below). 

Evidence that oxidized lipids play a role in the pathogenesis of RA comes from studies demonstrating the presence of lipid products arising from radical attack in rheumatoid synovial fluid. This is consistent with oxidation reactions occurring locally in the joint. Lipid peroxidation products that react with thiobarbituric acid (TBARs) have been detected in rheumatoid knee-joint synovial fluid (Rowley et /., 1984). In addition, the 

One technique to assess lipid peroxidation utilizes second-derivative spectrophotometric analysis of cyclohexane or ethanol-reconstituted extracts to determine the cis-trans and trans-trans isomeric forms of conjugated dienes and oxodiene species within synovial fluid. Using this method, a rise in the synovial fluid concentration of conjugated oxodienes, hydroxydienes and hydroperoxy-dienes was found to follow joint exercise (Merry et al., 1991). 

Single-pulse proton nuclear magnetic resonance (NMR) spectroscopy has been used to demonstrate that the mean chain length of synovial fluid triglycerides is shorter than that in corresponding sera (Naughton etal., 

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