Investigation of Lipid Metabolism in Dynamic Progression of Coronary Artery Atherosclerosis of Humans by Time-of-Flight Secondary Ion Mass Spectrometry

Abstract

Alterations in lipid metabolites in coronary artery tissues are phenotypic changes in the progression of atherosclerosis (AS). A full picture of the spatiotemporal distribution of lipid metabolites in coronary AS is needed for a deeper understanding of its pathology and the identification of potential biomarkers of disease progression. In this work, the changes in species, quantity, and distribution of lipid metabolites at different stages of AS, which were standardized by the disease areas, were analyzed through the high spatial resolution- and high sensitivity-time-of-flight secondary ion mass spectrometry (ToF-SIMS) under delayed extraction mode. Based on high lateral resolution imaging, we further analyzed the ToF-SIMS data extracted from the subregions of AS lesion tissues at different disease progression stages by semiquantitative comparison, clustering analysis (t-stochastic neighbor embedding and HCA), and KEGG enrichment. Thus, a much-detailed description of lipids’ features in coronary AS was achieved. We constructed a ToF-SIMS mass spectrometry database of coronary AS lipids. 40 specific lipid metabolites with distinctive patterns between different pathological stages were obtained. Chemical imaging unveiled further details regarding the spatial distribution of lipids. Moreover, linoleic acid and arachidonic acid metabolic pathway were predicted to be critical in AS progression.