Abstract
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.
Highlights
Atherosclerosis is the cause of more than 10 million deaths worldwide, and a major contributor to long-term morbidity and disability [1]
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 only looked at [M + Na]+, since it is the only ion that is stable in time of flight [33], and we found a coefficient of variation (CV) of 16%
Summary
Atherosclerosis is the cause of more than 10 million deaths worldwide, and a major contributor to long-term morbidity and disability [1]. This disease of the artery walls is characterized by the gradual formation of depositions in the vascular wall that are called atherosclerotic plaques. The mechanisms driving the evolution of a stable plaque to a vulnerable phenotype are not known in detail, it is clear that defective or unbalanced lipid transport plays a key role [5,6,7,8,9]. MALDI-MSI is suitable for the detection of small molecules, such as lipids
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