Work

Role of abnormal phosphatidylcholine metabolism in endoplasmic reticulum stress-induced carotid artery plaque destabilization

Year: 2026

Type: article

Abstract: The imbalance of carotid plaque stability is a key cause of acute cardiovascular and cerebrovascular events. Lipid metabolism disorder and endoplasmic reticulum stress (ERS) are both involved in the progression of atherosclerotic plaque. This study aims to reveal the role and molecular mechanism of abnormal phosphatidylcholine metabolism in ERS-induced carotid plaque instability, and to provide theoretical basis for plaque stabilization intervention. Methods With carotid plaques intima-media specimens as the research object, by HE staining is divided into a stable plaque group (group S) and unstable plaque group (U); The differences of metabolic profiles between the two groups were analyzed by principal component analysis (PCA) and orthogonal partial least squares-discriminant analysis (OPLS-DA). The differential metabolites were screened by cluster heat map and volcano map. Metabolic pathway enrichment analysis and IPA pathway analysis were used to identify key pathways. Finally, Western blot and RT-qPCR were used to verify the protein and mRNA expression levels of key molecules in ERS pathway. Two groups of baseline characteristics have no statistical difference (P > 0.05); PCA and OPLS-DA showed that the metabolic profiles of group S and group U were significantly separated. A total of 198 potential biomarkers were identified. Among them, changes in phospholipid metabolites (including phosphatidylcholine) were significant, and these are the core markers for differentiating plaque stability. Metabolic pathway enrichment analysis showed that glycerophospholipid metabolic pathway was the key core pathway regulating plaque stability. The protein and mRNA expressions of key molecules of ERS pathway (GRP78, ATF6, PERK, CHOP and IRE1) in group U were significantly higher than those in group S. Abnormal metabolism of phosphatidylcholine can drive the transformation of carotid plaques to an unstable phenotype by activating the ER stress (ERS) pathway (especially the PERK/CHOP branch pathway); this study verified the association mechanism between abnormal phosphatidylcholine metabolism and the activation of the ER stress pathway and the occurrence of unstable carotid plaques, providing experimental evidence for the study of the mechanism of unstable carotid plaques and the formulation of targeted clinical intervention strategies . • Focuses on the core issue of unstable carotid plaques, links abnormal phosphatidylcholine metabolism to related diseases, and offers new directions for cardiovascular and cerebrovascular health research. • Combines pathological classification, metabolomics and molecular biology techniques to verify core hypotheses multi-dimensionally, with comprehensive and reliable research methods. • Identifies 198 potential biomarkers, with significant changes in phospholipid metabolites, providing key basis for distinguishing plaque stability. • Confirms glycerophospholipid metabolism as the core pathway regulating plaque stability, locking key targets to support subsequent mechanism exploration. • Reveals that metabolic abnormalities affect plaque status by activating specific stress pathways, providing experimental support for developing targeted plaque-stabilizing interventions.

Source: Atherosclerosis Plus

DOI: 10.1016/j.athplu.2026.02.001