Work

Global lipidomic landscape of vulnerable carotid artery plaques: A preliminary analysis demonstrating proinflammatory features, apoptosis, and structural remodeling

Year: 2026

Type: article

Abstract: Background Plaque lipidomics generates molecular profiles that reflect plaque lipid metabolism and may reveal signatures of plaque vulnerability. Among lipid classes, ceramides and triglycerides (TAG) have been implicated in atherosclerosis, but their profiles in carotid plaque vulnerability have not been systematically evaluated. Objective By using liquid chromatography-tandem mass spectrometry (LC-MS/MS), untargeted global lipidomics was carried out to compare lipid profiles between vulnerable and nonvulnerable lesions as defined by magnetic resonance angiography with vessel wall imaging (MRA-VWI). Methods We performed a prospective single-center case-control study of plaque lipidomics comparing carotid plaques with and without vulnerable features as defined by MRA-VWI. Excised plaques were snap-frozen for lipidomics. Lipids were annotated and quantified using LC-MS/MS. Statistical analysis was performed to identify lipids showing significant differences between vulnerable and nonvulnerable plaques. Results Between April 2023 and August 2024, 28 patients were enrolled. A total of 400 lipid species across 27 subclasses from phospholipids, sphingolipids, fatty acids, sterols, and glycerides were characterized. Several classes of lipids including ceramides, hexosylceramides, monosialodihexosylganglioside, and TAGs were significantly higher in vulnerable plaques compared with nonvulnerable plaques. Conclusions Our findings highlight a distinct profiling of lipids in vulnerable plaques, which are associated with inflammation and structural remodeling. These lipid alterations may reflect biological processes involved in plaque destabilization and support lipidomics as a promising tool for biomarker discovery and potential therapeutic target in carotid artery disease. Clinical Relevance Assessment of plaque vulnerability is emerging as a clinically actionable strategy for risk stratification in extracranial carotid artery disease and stroke prevention. This study links in vivo magnetic resonance angiography with vessel wall imaging–defined vulnerability to an ex vivo lipidic profile, showing enrichment of ceramides, glycosphingolipids, gangliosides, and triglycerides in vulnerable carotid plaques. If validated, these lipid signatures could enable objective biomarkers to complement vessel wall imaging for risk stratification, timing of revascularization, and mechanistic targets for therapies aimed at plaque stabilization. Furthermore, this integrates imaging with lipid biology to advance precision vascular care.

Source: JVS Vascular Science

DOI: 10.1016/j.jvssci.2026.100421