Identification Of A High Density Lipoprotein Proteomic Signature Associated With Atherosclerosis Severity In Humans

High density lipoprotein associated cholesterol (HDL-C) has been the traditional biomarker for estimating cardiovascular protection derived from HDL; however, several recent studies have made it clear that HDL-C may not necessarily represent the protective capacity of HDL. The diverse protein and lipid content of HDL is becoming increasingly recognized as the basis for the functional complexity observed in these particles. Proteomics studies have identified 95 consensus proteins consistently found to associate with HDL. For the majority of these proteins, the functional importance of their association with HDL has not yet been determined. In this study, we tested the hypothesis that the protein composition of HDL will have an association with atherosclerosis burden in human subjects. A total of 101 subjects were selected based on atherosclerosis severity as determined by CT-angiography: normal (0% stenosis; n = 31), mild ( 70% stenosis; n = 9). HDL was separated from plasma by size-exclusion chromatography and isolated from pooled fractions, using a lipid binding resin. HDL bound proteins from each subject were analyzed by electrospray ionization tandem mass spectrometry and a spectral index value (derived from normalized spectrum counts and the number of subjects in which the peptide was detected) was used to examine the association between the HDL proteome and atherosclerosis severity. This analysis identified changes in 14 out of the total of 123 identified proteins. Of those that changed, some displayed clear correlations with disease severity, whereas others were only affected in the severe disease group. Some of these proteins have been previously suggested to play a role in the interaction of HDL and atherosclerosis, such as apoA-IV (+20%; p