Targeted profiling of atherogenic phospholipids in human plasma and lipoproteins of hyperlipidemic patients using MALDI-QIT-TOF-MS/MS

Atherosclerosis. 2012 Sep;224(1):177-86. doi: 10.1016/j.atherosclerosis.2012.06.010. Epub 2012 Jun 23.

Abstract

Objectives: Phospholipids (PLs) are increasingly recognized as key molecules with potential diagnostic value in acute inflammation, CVD and atherosclerosis. We introduce a pioneer mass spectrometry (MS)-based approach aiming to investigate the relationship of specific plasma PL-subsets with atherogenic blood parameters in young patients with familial hyperlipidemia representing high-CVD-risk groups.

Methods: Plasma of carefully phenotyped FH and FCH patients as well as normolipidemic subjects (age 13 ± 5 years, n = 20) was used. Clinical parameters were assessed using standard laboratory techniques and lipids were subjected to a direct targeted monitoring using LC-ESI-SRM- and MALDI-QIT-TOF-MS/MS, respectively. Statistical analysis was performed to evaluate correlations between PL data and the clinical parameters.

Results: Most characteristically significant differences of SM/PC and PC/LPC ratios and positive correlations between SM vs. LDL-C (r = 0.946; p = 0.004) and LPC vs. VLDL-C (r = 0.669; p = 0.218) were observed in FH in contrast to the other study groups. OxPC levels were found in the range of ∼2-20 μmol/L with predominance of short-chain aldehydic species (e.g. SOVPC). A positive correlation of OxPCs with IMT (r = 0.952; p = 0.052) and HDL-C (r = 0.893; p = 0.016) but negative correlation with OxLDL (r = -0.910; p = 0.096) was observed.

Conclusions: Our study was a first attempt to use a MALDI-QIT-TOF-MS/MS based clinical lipidomics approach to investigate atherogenic dyslipidemia in young patients with familial hyperlipidemia. This technique represents a promising platform for clinical screening of lipid biomarkers in the future.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Atherosclerosis / blood
  • Biomarkers / blood
  • Child
  • Cholesterol, LDL
  • Female
  • Humans
  • Hyperlipidemia, Familial Combined / blood*
  • Hyperlipoproteinemia Type II / blood*
  • Lipoproteins / blood*
  • Lysophosphatidylcholines / blood
  • Male
  • Phosphatidylcholines / blood
  • Phospholipids / blood*
  • Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization / methods
  • Sphingomyelins / blood
  • Tandem Mass Spectrometry
  • Young Adult

Substances

  • Biomarkers
  • Cholesterol, LDL
  • Lipoproteins
  • Lysophosphatidylcholines
  • Phosphatidylcholines
  • Phospholipids
  • Sphingomyelins