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We sought to perform a systematic lipid analysis of atherosclerotic plaques using emerging mass spectrometry techniques.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.This comprehensive analysis of plaque lipids demonstrates the potential of lipidomics for unraveling the lipid heterogeneity within atherosclerotic lesions.

Original publication

DOI

10.1161/circgenetics.110.959098

Type

Journal article

Journal

Circulation. Cardiovascular genetics

Publication Date

06/2011

Volume

4

Pages

232 - 242

Addresses

King's British Heart Foundation Centre, King's College, London, UK.

Keywords

Radial Artery, Humans, Lipids, Endarterectomy, Carotid, Principal Component Analysis, Software, Atherosclerosis, Lipid Metabolism, Mass Spectrometry, Plaque, Atherosclerotic