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Quantifying HDL proteins by mass spectrometry: how many proteins are there and what are their functions?
1a Department of Medicine , University of Washington , Seattle , WA , USA.
Insights
High-density lipoprotein (HDL) cholesterol
Area of Science:
- Biochemistry
- Proteomics
- Cardiovascular Disease Research
Background:
- Low levels of high-density lipoprotein (HDL) cholesterol are linked to increased cardiovascular disease (CVD) risk.
- Recent studies question whether increasing HDL cholesterol levels reduces CVD risk in statin-treated patients with atherosclerosis.
Purpose of the Study:
- To explore quantitative MS/MS-based HDL proteomics as a method to identify new HDL metrics.
- To discuss the feasibility and challenges of using HDL proteomics in translational studies.
- To examine how lipid-lowering therapy and renal disease affect HDL function and proteome.
Main Methods:
- Quantitative MS/MS-based proteomics to analyze HDL protein cargo.
- Review of recent translational studies on HDL proteomics.
- Analysis of HDL alterations in the context of lipid-lowering therapy and renal disease.
Main Results:
- HDL contains a diverse proteome, with MS/MS analysis identifying over 80 different proteins.
- HDL's functions extend beyond lipid transport, involving a wide range of protein interactions.
- Challenges exist in confirming protein association with HDL, functional significance, and reproducibility in biomarker detection.
Conclusions:
- HDL possesses a complex protein cargo with functions beyond traditional lipid transport.
- Quantitative MS/MS-based HDL proteomics offers a promising avenue for discovering novel cardioprotective biomarkers.
- Further research is needed to overcome challenges in validating HDL-associated proteins and their role in disease risk.
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.
