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HDL quality features revealed by proteome‒lipidome connectivity are associated with atherosclerotic disease

Dandan Wang1, Bilian Yu2, Qingrun Li1

  • 1CAS Key Laboratory of Systems Biology, CAS Center for Excellence in Molecular Cell Science, Shanghai Institute of Biochemistry and Cell Biology, Chinese Academy of Sciences, Shanghai 200031, China.

Journal of Molecular Cell Biology
|March 12, 2022
PubMed

Insights

We developed high-resolution proteomics and lipidomics (HiPL) to analyze lipoprotein and high-density lipoprotein (HDL) particle composition. This method reveals proteome-lipidome connectivity (PLC) crucial for understanding cardiovascular disease (CVD) and diagnosing acute coronary syndrome (ACS).

Area of Science:

  • Biochemistry
  • Cardiovascular Research
  • Proteomics and Lipidomics

Background:

  • Lipoprotein particles, including high-density lipoprotein (HDL), consist of diverse protein and lipid subgroups.
  • The molecular composition of these subgroups is intrinsically linked to cardiovascular disease (CVD) risk.
  • Understanding these complex molecular distributions is essential for advancing CVD diagnostics and therapeutics.

Purpose of the Study:

  • To establish novel high-resolution proteomics and lipidomics (HiPL) methods for detailed molecular profiling of lipoprotein and HDL subgroups.
  • To investigate the proteome-lipidome connectivity (PLC) within lipoprotein and HDL particles.
  • To assess the potential of HiPL and PLC features in diagnosing conditions like acute coronary syndrome (ACS).

Main Methods:

  • Development of optimized anion-exchange chromatography for high-resolution separation of lipoprotein and HDL subgroups.
  • Comprehensive omics-level quantification of proteins and lipids within these resolved subgroups.
  • Pearson correlation coefficient analysis to determine proteome-lipidome connectivity (PLC) across subgroups.

Main Results:

  • The established HiPL methods successfully depicted detailed molecular profiles across lipoprotein and HDL subgroups.
  • Analysis revealed the dynamics of molecular profiles and particle reconstruction in response to high-fat, high-cholesterol diets and in ACS patients.
  • HDL-specific PLC features demonstrated superior discrimination of ACS patients from healthy individuals compared to direct omics or general lipoprotein PLC.

Conclusions:

  • The developed HiPL methods provide unprecedented insights into the molecular dynamics and composition of lipoprotein and HDL particles.
  • Proteome-lipidome connectivity (PLC) analysis offers a novel approach to understanding lipoprotein behavior in disease states.
  • HDL-HiPL-derived PLC features show significant potential as a diagnostic biomarker for acute coronary syndrome (ACS).

Keywords:
HDLatherosclerotic diseasehigh resolutionlipidomicsproteomics

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