Lipidomic Expression Analysis in Carotid Atherosclerotic Disease: A Systematic Review

Background: Lipids are key molecules for atherosclerosis, with tight regulation mechanisms, making them potential biomarkers for disease-specific diagnostics and therapeutics. Therefore, we aim to perform a systematic literature review on lipidomic analysis in serum/plasma and plaque samples of patients with carotid atherosclerosis. Methods: We performed a systematic review following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines on the lipidomic profile in serum/plasma and carotid artery plaques from patients with significant carotid disease by degree of stenosis in preoperative imaging and clinical presentation (symptomatic, asymptomatic, and radiation-induced carotid disease). Main outcome was the differential lipidomic expression of serum/plasma, and plaque lipids of patients with carotid artery atherosclerosis. Studies were screened using the Newcastle-Ottawa Scale to determine the quality of the design and content of the selected manuscripts. Results: We included fourteen studies, from which ten included plaque analysis. The lipidomic analysis revealed that sterols and hydroxycholesterols were consistently found in both blood and plaque across studies. Triacylglycerols were present in both sample types, with specific forms linked to radiation-induced carotid artery disease. Symptomatic patients exhibited esterified hydroxyeicosatetraenoic acids and arachidonic acid precursors exclusively in plaque with an inflammatory profile of the disease. In contrast, docosahexaenoic acid and eicosapentaenoic acid were associated with plaque stability. Diabetics showed nonesterified fatty acids and specific phospholipids only in plaque, indicating localized lipid changes. Other pathways relevant to disease progression include the sphingolipids and ceramide pathways with inflammatory profiling. Conclusion: Lipidomic provides an innovative approach to stratify carotid atherosclerotic disease. Integrating lipidomic data with other -omics approaches may further enhance our understanding of disease mechanisms and aid in the development of precision medicine approaches, specifically in those patients at risk for early carotid atherosclerotic disease.