Targeted profiling of atherogenic phospholipids in human plasma and lipoproteins of hyperlipidemic patients using MALDI-QIT-TOF-MS/MS.
OBJECTIVE
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.
Center for Physiology and Pharmacology, Medical University of Vienna, Schwarzspanierstaße 17, A-1090 Vienna, Austria. gerald.stubiger@meduniwien.ac.at
Gerald
G
Stübiger
Elsie
E
Aldover-Macasaet
Wolfgang
W
Bicker
Grazyna
G
Sobal
Andrea
A
Willfort-Ehringer
Katharina
K
Pock
Valery
V
Bochkov
Kurt
K
Widhalm
Omar
O
Belgacem
D000293:Adolescent; D050197:Atherosclerosis / Q000097:blood; D015415:Biomarkers / Q000097:blood; D002648:Child; D008078:Cholesterol, LDL; D005260:Female; D006801:Humans; D006950:Hyperlipidemia, Familial Combined / Q000097:blood*; D006938:Hyperlipoproteinemia Type II / Q000097:blood*; D008074:Lipoproteins / Q000097:blood*; D008244:Lysophosphatidylcholines / Q000097:blood; D008297:Male; D010713:Phosphatidylcholines / Q000097:blood; D010743:Phospholipids / Q000097:blood*; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization / Q000379:methods; D013109:Sphingomyelins / Q000097:blood; D053719:Tandem Mass Spectrometry; D055815:Young Adult
D015415:Biomarkers; D008078:Cholesterol, LDL; D008074:Lipoproteins; D008244:Lysophosphatidylcholines; D010713:Phosphatidylcholines; D010743:Phospholipids; D013109:Sphingomyelins