Lipoprotein Oxidation Products and Arteriosclerosis: Theory and Methods with Applicability to the Clinical Chemistry Laboratory

Abstract

Although it is not yet conclusively proven that oxidation is the cause of arteriosclerosis in humans. Animal experiments in the form of transgenic and knockout mice models support this hypothesis. If this relationship can be conclusively demonstrated, it is likely there will be a need to measure lipoprotein oxidation products in the clinical laboratory for risk assessment. Native low-density lipoproteins (LDL) are heterogeneous and contain huge numbers of oxidation sensitive components from which a vast number of oxidation products can be produced. Thus, largely for research purposes, but also to develop approaches for risk assessment, many methods have been developed for measuring oxidation products. Although some of the measurement techniques have application for research laboratories only, others are appropriate for use in clinical laboratories and some appear to have adaptability for automation. The oxidation on products reflecting molecular modifications within the lipids and proteins of LDL, breakdown products of the lipids and proteins, and measurement of whole LDL modified by oxidation are also discussed in this chapter. To date, the failure of randomized trials with antioxidant nutrients to retard arteriosclerosis has made it clear that demonstrating a definite relationship in humans may be more difficult than expected. Many of these methods are straightforward enough to be adapted for routine clinical laboratory use should the need arise at a later time and should they prove effective. Alternatively, ELISA for OxLDL may be valuable for risk assessment, but because of the complexity of OxLDL, applied research is needed to determine how best to use monoclonal antibodies to measure OxLDL and how best to standardize the assays.