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Expert Rev Proteomics. 2018 Jan;15(1):31-40. doi: 10.1080/14789450.2018.1402680. Epub 2017 Nov 13.

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

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a Department of Medicine , University of Washington , Seattle , WA , USA.


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.


Apolipoprotein A-I; biomarker; dysfunctional HDL; lipid-lowering therapy; parallel reaction monitoring; renal disease; selected reaction monitoring; shotgun proteomics

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