Quantifying HDL proteins by mass spectrometry: how many proteins are there and what are their functions?

INTRODUCTION: Many lines of evidence indicate that low levels of HDL cholesterol increase the risk of cardiovascular disease (CVD). However, recent clinical studies of statin-treated subjects with established atherosclerosis cast doubt on the hypothesis that elevating HDL cholesterol levels reduces CVD risk. Areas covered: It is critical to identify new HDL metrics that capture HDL's proposed cardioprotective effects. One promising approach is quantitative MS/MS-based HDL proteomics. This article focuses on recent studies of the feasibility and challenges of using this strategy in translational studies. It also discusses how lipid-lowering therapy and renal disease alter HDL's functions and proteome, and how HDL might serve as a platform for binding proteins with specific functional properties. Expert commentary: It is clear that HDL has a diverse protein cargo and that its functions extend well beyond its classic role in lipid transport and reverse cholesterol transport. MS/MS analysis has demonstrated that HDL might contain >80 different proteins. Key challenges are demonstrating that these proteins truly associate with HDL, are functionally important, and that MS-based HDL proteomics can reproducibly detect biomarkers in translational studies of disease risk.