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Updated: Jul 4, 2026
Deep Proteome Profiling by Isobaric Labeling, Extensive Liquid Chromatography, Mass Spectrometry, and Software-assisted Quantification
Published on: November 15, 2017
HDL proteomics: pot of gold or Pandora's box?
Muredach P Reilly1, Alan R Tall
1Cardiovascular Institute, Department of Medicine, University of Pennsylvania Medical Center, Philadelphia, PA 19104-6160, USA. muredach@itmat.gcrc.upenn.edu
Insights
High-density lipoprotein (HDL) is unexpectedly rich in proteins regulating innate immunity and inflammation. This finding suggests HDL plays a key role in immune responses and may offer new avenues for cardiovascular disease research.
Area of Science:
- Cardiovascular Science
- Proteomics
- Immunology
Background:
- High-density lipoprotein (HDL) is traditionally known for its role in reverse cholesterol transport.
- The comprehensive protein composition of HDL and its functional implications remain incompletely understood.
Discussion:
- Vaisar et al. investigated the proteome of HDL, revealing an enrichment of complement cascade proteins and protease inhibitors.
- These findings suggest HDL participates in innate immunity and regulates inflammatory and coagulation processes.
- Alterations in HDL protein composition were observed in patients with coronary artery disease.
Key Insights:
- HDL possesses previously unrecognized functions beyond cholesterol transport, including roles in innate immunity and inflammation regulation.
- The study highlights the potential of HDL proteomics to uncover novel biological mechanisms.
- HDL protein profiles may be altered in cardiovascular disease.
Outlook:
- Further validation using standardized methods and larger clinical cohorts is necessary.
- HDL proteomics could lead to the development of biomarkers for predicting therapeutic intervention outcomes.
- This research opens new avenues for understanding HDL's role in atherosclerosis and its complications.
Abstract:
In this issue of the JCI, Vaisar et al. studied the proteome of HDL (see the related article beginning on page 746). They reveal, quite unexpectedly, that HDL is enriched in several proteins involved in the complement cascade, as well as in a variety of protease inhibitors, supporting the concept that HDL plays a role in innate immunity and in the regulation of proteolytic cascades involved in inflammatory and coagulation processes. The protein makeup of HDL also appears to be altered in patients with coronary artery disease. HDL proteomics is in its infancy, and preliminary findings will need to be confirmed using standardized approaches in larger clinical samples. However, this approach promises to better elucidate the relationship of HDL to atherosclerosis and its complications and could eventually help in the development of biomarkers to predict the outcome of interventions that alter HDL levels and functions.
