Abstract
AbstractCarotid atherosclerosis is a risk factor for ischemic stroke, one of the main causes of mortality and disability worldwide. The disease is characterized by plaques, heterogeneous deposits of lipids, and necrotic debris in the vascular wall, which grow gradually and may remain asymptomatic for decades. However, at some point a plaque can evolve to a high-risk plaque phenotype, which may trigger a cerebrovascular event. Lipids play a key role in the development and progression of atherosclerosis, but the nature of their involvement is not fully understood. Using matrix-assisted laser desorption/ionization mass spectrometry imaging, we visualized the distribution of approximately 200 different lipid signals, originating of >90 uniquely assigned species, in 106 tissue sections of 12 human carotid atherosclerotic plaques. We performed unsupervised classification of the mass spectrometry dataset, as well as a histology-directed multivariate analysis. These data allowed us to extract the spatial lipid patterns associated with morphological plaque features in advanced plaques from a symptomatic population, revealing spatial lipid patterns in atherosclerosis and their relation to histological tissue type. The abundances of sphingomyelin and oxidized cholesteryl ester species were elevated specifically in necrotic intima areas, whereas diacylglycerols and triacylglycerols were spatially correlated to areas containing the coagulation protein fibrin. These results demonstrate a clear colocalization between plaque features and specific lipid classes, as well as individual lipid species in high-risk atherosclerotic plaques.
Highlights
Carotid atherosclerosis is a risk factor for ischemic stroke, one of the main causes of mortality and disability worldwide
Twelve human carotid endarterectomy samples were processed into a series of 106 axial tissue sections to be imaged by MALDI-mass spectrometry imaging (MSI) and histology
Processing of MALDI-MSI data resulted in lipid images of 194 lipidrelated signals of which 93 were uniquely identified or assigned lipid species, see supplemental Table S3
Summary
Carotid atherosclerosis is a risk factor for ischemic stroke, one of the main causes of mortality and disability worldwide. We processed tissue sections adjacent to those studied by MSI for a series of histological staining procedures to identify compositional features of plaque vulnerability, i.e., necrotic core, the thrombus-associated protein fibrin, erythrocytes, and foam cells [20,21,22]. In this way we were able to compare spatial lipid patterns with gold standard histological assessment of plaque composition. We considered the histological results and investigated correlations between lipids and compositional features of plaque vulnerability
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