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Published on: October 12, 2017
Shotgun proteomics implicates protease inhibition and complement activation in the antiinflammatory properties of HDL
Tomas Vaisar1, Subramaniam Pennathur, Pattie S Green
1Department of Medicine, University of Washington School of Medicine, Seattle, Washington 98195, USA.
Insights
High-density lipoprotein (HDL) offers cardioprotection beyond cholesterol transport. This study reveals HDL carries proteins that regulate complement and inflammation, suggesting novel antiatherosclerotic roles.
Area of Science:
- Cardiovascular Biology
- Proteomics
- Immunology
Background:
- High-density lipoprotein (HDL) is known to reduce atherosclerotic cardiovascular disease (CVD) risk by facilitating cholesterol removal from macrophage foam cells.
- However, the full spectrum of HDL's antiatherosclerotic mechanisms remains incompletely understood.
- Investigating HDL's protein cargo may uncover novel cardioprotective functions.
Purpose of the Study:
- To explore the protein composition of HDL in healthy individuals and those with coronary artery disease (CAD).
- To identify potential novel cardioprotective proteins carried by HDL.
- To test the hypothesis that HDL's protein cargo contributes to its anti-inflammatory and antiatherogenic properties.
Main Methods:
- Shotgun proteomics was employed to analyze HDL isolated from healthy subjects and CAD patients.
- Mass spectrometry and biochemical assays were utilized to characterize HDL composition.
- Comparative analysis of HDL proteomes between disease and control groups.
Main Results:
- HDL was found to contain multiple complement-regulatory proteins and various serpins (serine-type endopeptidase inhibitors).
- Numerous acute-phase response proteins were identified, supporting HDL's role in inflammation.
- HDL3 from CAD patients showed selective enrichment of apolipoprotein E (apoE).
Conclusions:
- HDL possesses previously unrecognized functions in regulating the complement system and protecting tissues from proteolysis.
- The protein cargo of HDL significantly contributes to its anti-inflammatory and antiatherogenic effects.
- HDL may play a critical role in managing inflammation and protecting against cardiovascular disease through its diverse protein components.
Abstract:
HDL lowers the risk for atherosclerotic cardiovascular disease by promoting cholesterol efflux from macrophage foam cells. However, other antiatherosclerotic properties of HDL are poorly understood. To test the hypothesis that the lipoprotein carries proteins that might have novel cardioprotective activities, we used shotgun proteomics to investigate the composition of HDL isolated from healthy subjects and subjects with coronary artery disease (CAD). Unexpectedly, our analytical strategy identified multiple complement-regulatory proteins and a diverse array of distinct serpins with serine-type endopeptidase inhibitor activity. Many acute-phase response proteins were also detected, supporting the proposal that HDL is of central importance in inflammation. Mass spectrometry and biochemical analyses demonstrated that HDL3 from subjects with CAD was selectively enriched in apoE, raising the possibility that HDL carries a unique cargo of proteins in humans with clinically significant cardiovascular disease. Collectively, our observations suggest that HDL plays previously unsuspected roles in regulating the complement system and protecting tissue from proteolysis and that the protein cargo of HDL contributes to its antiinflammatory and antiatherogenic properties.
