A lipid atlas of human carotid atherosclerosis

Carotid atherosclerosis is one of the main causes of stroke, mortality and disability worldwide. The disease is characterized by plaques, heterogeneous depositions 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. Using matrix-assisted laser desorption/ionization mass spectrometry imaging, we visualized the distribution of approximately 200 lipids in 106 tissue sections of 12 human carotid atherosclerotic plaques. We performed unsupervised classification of the mass spectrometry dataset, as well as a histology-driven multivariate analysis. These data allowed us to compare the spatial lipid patterns with morphological plaque features that have been associated with enhanced risk of symptoms. The abundances of sphingomyelin and oxidized cholesteryl ester species were elevated specifically in necrotic intima areas, while diacylglycerols and triacylglycerols were spatially correlated to areas containing the coagulation protein fibrin. This is the first study to systematically investigate spatial lipid patterns in atherosclerosis, analyze their relation to histological tissue type, and to demonstrate a clear co-localization between plaque features and specific lipid classes and individual lipid molecules in high-risk atherosclerotic plaques.