Spatial metabolomics identifies lipid profiles of human carotid atherosclerosis

Background and aims Carotid atherosclerosis is an important cause of ischemic stroke. Lipids play a key role in the progression of atherosclerosis. To date, the spatial lipid profile of carotid atherosclerotic plaques related to histology has not been systematically investigated. Methods Carotid atherosclerosis samples from 12 patients were obtained and classified into four classical pathological stages (preatheroma, atheroma, fibroatheroma and complicated lesion) by histological staining. Desorption electrospray ionization-mass spectrometry imaging (DESI-MSI) was used to investigate the lipid profile of carotid atherosclerosis, and correlated it with histological information. Bioinformatics technology was used to process MSI data among different pathological stages of atherosclerosis lesions. Results A total of 55 lipids (26 throughout cross-section regions [TCSRs], 13 in lipid-rich regions [LRRs], and 16 in collagen-rich regions [CRRs]) were initially identified in carotid plaque from one patient. Subsequently, 32 of 55 lipids (12 in TCSRs, eight in LRRs, and 12 in CRRs) were further screened in 11 patients. Pathway enrichment analysis showed that multiple metabolic pathways, such as fat digestion and absorption, cholesterol metabolism, lipid and atherosclerosis, were enriched in TCSRs; sphingolipid signaling pathway, necroptosis pathway were enriched in LRRs; and glycerophospholipid metabolism, ether lipid metabolism pathway were mainly enriched in CRRs. Conclusions This study comprehensively showed the spatial lipid metabolism footprint in human carotid atherosclerotic plaques. The lipid profiles and related metabolism pathways in three regions of plaque with disease progression were different markedly, suggesting that the different metabolic mechanisms in these regions of carotid plaque may be critical in atherosclerosis progression.