Atherosclerosis is a lipid and inflammation-driven disease of the arteries that is characterized by gradual buildup of plaques in the vascular wall. A so-called vulnerable plaque, consisting of a lipid-rich necrotic core contained by a thin fibrous cap, may rupture and trigger thrombus formation, which can lead to ischemia in the heart (heart attack) or in the brain (stroke). In this study, we present a protocol to investigate the lipid composition of advanced human carotid plaques using matrix-assisted laser desorption ionization (MALDI) mass spectrometry imaging (MSI), providing a framework that should enable the discrimination of vulnerable from stable plaques based on lipid composition. We optimized the tissue preparation and imaging methods by systematically analyzing data from three specimens: two human carotid endarterectomy samples (advanced plaque) and one autopsy sample (early stage plaque). We show a robust data reduction method and evaluate the variability of the endarterectomy samples. We found diacylglycerols to be more abundant in a thrombotic area compared to other plaque areas and could distinguish advanced plaque from early stage plaque based on cholesteryl ester composition. We plan to use this systematic approach to analyze a larger dataset of carotid atherosclerotic plaques. [Figure not available: see fulltext.].

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Keywords Artherosclerosis, Carotid artery, Endarterectomy, Imaging, Lipids, MALDI-MSI, Mass spectrometry, Method, Plaque, Thrombus, Vulnerable plaque
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Journal Journal of the American Society for Mass Spectrometry
Visscher, M. (Mirjam), Moerman, A.M. (Astrid M.), Burgers, P.C, van Beusekom, H.M.M, Luider, T.M, Verhagen, H.J.M, … van Soest, G. (2019). Data Processing Pipeline for Lipid Profiling of Carotid Atherosclerotic Plaque with Mass Spectrometry Imaging. Journal of the American Society for Mass Spectrometry. doi:10.1007/s13361-019-02254-y