When good cholesterol goes bad: Mass spectrometric approaches for the analysis of dysfunctional HDL

TOXI 125

Jay Heinecke, heinecke@u.washington.edu, Department of Medicine, University of Washington, Box 356426, HSB BB545, University of Washington, Seattle, WA 98195
Posttranslational oxidative modifications of lipoproteins are implicated in the pathogenesis of atherosclerotic vascular disease. Electrospray ionization tandem mass spectrometry (ESI-MS/MS) coupled with liquid chromatography is rapidly emerging as a powerful technique for pinpointing sites of amino acid oxidation within apolipoproteins. Oxidants generated by myeloperoxidase lead to the site specific oxidation apolipoprotein A-I – the major protein in HDL, and these posttranslational modifications are associated with major impacts on the biological function. We have recently used 2-dimensional liquid chromatography ESI-MS/MS to test the hypothesis that proteins implicated in inflammation might be enriched in the HDL of subjects with coronary artery disease (CAD). Our observations suggest that HDL carries a unique cargo of proteins in CAD subjects and that certain of these proteins might make previously unsuspected contributions to the anti-inflammatory properties of HDL.