Circ Cardiovasc Genet. 2011 Jun;4(3):232-42. doi: 10.1161/CIRCGENETICS.110.959098. Epub 2011 Apr 21. Comparative lipidomics profiling of human atherosclerotic plaques. Stegemann C1, Drozdov I, Shalhoub J, Humphries J, Ladroue C, Didangelos A, Baumert M, Allen M, Davies AH, Monaco C, Smith A, Xu Q, Mayr M. Author information   Abstract BACKGROUND:

We sought to perform a systematic lipid analysis of atherosclerotic plaques using emerging mass spectrometry techniques.

METHODS AND RESULTS:

A chip-based robotic nanoelectrospray platform interfaced to a triple quadrupole mass spectrometer was adapted to analyze lipids in tissue sections and extracts from human endarterectomy specimens by shotgun lipidomics. Eighteen scans for different lipid classes plus additional scans for fatty acids resulted in the detection of 150 lipid species from 9 different classes of which 24 were detected in endarterectomies only. Further analyses focused on plaques from symptomatic and asymptomatic patients and stable versus unstable regions within the same lesion. Polyunsaturated cholesteryl esters with long-chain fatty acids and certain sphingomyelin species showed the greatest relative enrichment in plaques compared to plasma and formed part of a lipid signature for vulnerable and stable plaque areas in a systems-wide network analysis. In principal component analyses, the combination of lipid species across different classes provided a better separation of stable and unstable areas than individual lipid classes.

CONCLUSIONS:

This comprehensive analysis of plaque lipids demonstrates the potential of lipidomics for unraveling the lipid heterogeneity within atherosclerotic lesions.

Liquid extraction surface analysis (LESA) coupled to nano-ESI-MS. Frozen human plaques were cut at 200 μm using a rotary microtome (Microm HM560 cryostat, Thermo Scientific), placed on electrostatically charged slides (Superfrost Plus, BDH) and air dried for 15–30 min. Lipids were directly analyzed from tissue sections with a Advion TriVersa NanoMate system (Advion BioSciences Inc., Ithaca, NY) controlled by Chipsoft software (v8.1.0.928, Advion BioSciences) coupled to a triple quadrupole mass spectrometer (QqQ-MS, TSQ Vantage, Thermo Fisher Scientific, UK).