Targeted profiling of atherogenic phospholipids in human plasma and lipoproteins of hyperlipidemic patients using MALDI-QIT-TOF-MS/MS |
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Authors: | Gerald Stübiger Elsie Aldover-Macasaet Wolfgang Bicker Grazyna Sobal Andrea Willfort-Ehringer Katharina Pock Valery Bochkov Kurt Widhalm Omar Belgacem |
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Institution: | 1. Center for Physiology and Pharmacology, Medical University of Vienna, Schwarzspanierstaße 17, A-1090 Vienna, Austria;2. Department of Pediatrics and Adolescent Medicine, Medical University of Vienna, Währinger Gürtel 18-20, A-1090 Vienna, Austria;3. FTC-Forensic-Toxicological Laboratory Ltd., Simmeringer Hauptstraße 24, A-1110 Vienna, Austria;4. Department of Nuclear Medicine, Medical University of Vienna, Währinger Gürtel 18-20, A-1090 Vienna, Austria;5. Department of Angiology, Medical University of Vienna, Währinger Gürtel 18-20, A-1090 Vienna, Austria;6. Octapharma Pharmazeutika Produktionsges.m.b.H, Oberlaaerstrasse 235, A-1100 Vienna, Austria;7. Shimadzu, Wharfside, Trafford Wharf Road, Manchester M17 1GP, England, UK |
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Abstract: | ObjectivesPhospholipids (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.MethodsPlasma 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.ResultsMost 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.ConclusionsOur 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. |
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