Cardiovascular disease is the leading cause of death world wide according to the World Health Organization. USA Today recently reported that 2200 Americans die every day from heart disease. The most common cause of heart disease is atherosclerosis. It has been extensively reported that oxidatively modified low density lipoprotein (LDL) play a key role in the initiation and progression of atherosclerosis.Our lab has oxidized LDL with copper, hypochlorite, and superoxide, respectively, and formulated a direct comparison of lipid peroxidation generated by these relevant oxidants. Thiobarbituric acid reactive substances assay (TBARS) is a widely used method for estimating oxidative stress and assessing lipid peroxidation of LDL. Copper, hypochlorite, and superoxide mediated oxidation of LDL in our lab revealed that low micromolar concentrations of copper were sufficient to generate substantial lipid oxidation, while superoxide and hypochlorite required much higher doses. Copper and superoxide dosing showed a linear dose response, while hypochlorite required millimoloar concentrations to generate lipid oxidation and quickly reached a maximum of lipid peroxide products. Furthermore, hypochlorite was shown to have an inhibitory effect on oxidation when copper, hypochlorite, and superoxide were simultaneously reacted with LDL.LDL contains one monomeric protein, apolipoprotein B 100 (apoB), which, like the lipid portion, can become modified by the oxidants copper, hypochlorite, and superoxide. This work utilized a precipitation method and a gel absorption approach coupled with LC-MS-MS to identify sites of apoB oxidation as well as the type of oxidation. Protein modifications identified include: methionine oxidation, proline oxidation, and conjugates of lipid peroxidation products to lysine, arginine, and tryptophan.  Study of both lipid and protein oxidation will allow correlations between oxidant type, oxidant dose, and lipid peroxidation with apoB modifications.

Correlating apolipoprotein B 100 modifications with oxidant type, oxidant dose, and lipid peroxidation

247th National Meeting (2014)

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