Abstract 20523: Comparative Lipidomics Profiling of Human Atherosclerotic Plaques
Background: Lipid accumulation within large arteries is the hallmark of atherosclerosis, but no comparative lipidomics analysis using the latest mass spectrometry (MS) techniques has been reported to date.
Methods and results: Lipid profiling of radial arteries, carotid and femoral endarterectomies was performed by ultra performance liquid chromatography MS. Lipid species were subsequently identified by shotgun lipidomics using a high-sensitivity triple quadrupole MS. 22 different scans in positive and negative ion mode plus additional scans for different fatty acids resulted in the detection of 149 lipid species from 9 different classes, of which 28 were found in endarterectomies only. Comparative analysis of both datasets revealed that most of the information was among lysophosphatidylcholines, sphingomyelins and cholesteryl esters (CE), including two oxidised CE species. Further analyses focused on plaques from symptomatic and asymptomatic patients (n=6). Again, among all the lipids analysed most of the information was contained in CEs with significant contributions from sphingomyelins, but the distance between plaques from symptomatic and asymptomatic patients in principal component analysis was negligible. In comparison with previous studies, however, the sensitivity of the MS approach allowed the detection of additional CE species in plaques and plasma. Within the class of CEs, polyunsaturated species with long chain fatty acids showed the greatest dynamic and relative enrichment in plaques compared to plasma. In a third analysis, we investigated lipids of stable and unstable regions from the same lesion (n=5), thereby providing an internal control for each sample and minimizing interpatient variability. In this analysis, a clear separation was obtained and shotgun lipidomics identified an unanticipated lipid signature of vulnerable and stable plaque areas in patients on statin treatment.
Conclusion: This study provides the most comprehensive MS analysis of plaque lipids to date. Our results demonstrate the potential of advanced lipidomics profiling for unravelling the lipid heterogeneity within atherosclerotic lesions and suggest that these emerging metabolomic tools may be used for diagnostic purposes or drug screening.
- © 2010 by American Heart Association, Inc.