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TWIST1 drives endothelial-to-mesenchymal-transition to stabilize atherosclerotic plaques [single cell RNA-seq]

ABSTRACT: Single cell RNA sequencing (scRNA-seq) was used to analyse the diversity of ECs in the atherosclerotic mouse aorta, as well as the effect of endothelial-specific Twist1 deletion on aortic endothelial cells in mice exposed to a high fat diet.

ORGANISM(S): Mus musculus

PROVIDER: GSE278596 | GEO | 2026/01/12

REPOSITORIES: GEO

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Project description:BACKGROUND AND AIMS: Atherosclerosis, characterized by dysfunction of lipid metabolism and chronic inflammation, is considered as a metabolic disorder as well as a major contributor to cardiovascular diseases. However, metabolic signatures of atherosclerosis have not been well explored. Thus, this study aim to reveal some promising biomarkers associated with phospholipid-related metabolites in rabbit atherosclerotic plaques by conducting integrated proteomic and metabolic analyses.METHODS: New Zealand white rabbits were randomly divided into the model group injured by the balloon and the sham group with incisions. Abdominal aortas were collected from the two groups, and were prepared using a new approach, which applies proteinase K during the sample preparation procedure to increase the metabolite coverage. Then, a Tandem Mass Tags (TMT)-labeled quantitative proteomic analysis and an untargeted metabolomics analysis via liquid chromatography-mass spectrometry (LC-MS) of abdominal aortas were applied to evaluate the possible fingerprints of arterial plaques on the protein and metabolite levels. Then, the correlation between differentially expressed proteins and differentially expressed metabolites was analysed based on the Pearson correlation coefficient strategy. Acquired data were subsequently analyzed with the use of both uni‐ and multi-variate statistics.RESULTS: Advanced atherosclerotic plaques developed in the model group. A total of 207 proteins were found to be significantly altered in the injured aorta compared to the uninjured aorta, with 133 upregulated proteins and 74 downregulated proteins (fold changes > 1.2, P < 0.05). 234 metabolites were discovered to be significantly altered in plaques under the positive ion mode and 187 metabolites under the negative ion mode. These metabolites were mainly related to the phospholipid metabolic pathways. In this study, decreases were found in the phosphatidylcholines (PCs) [PC(32:0), PC(40:7), PC(42:7)], phosphatidylethanolamine PE(18:0/18:2), lysophosphatidylethanolamines (LPEs) [LPE(22:6), LPE(18:2), LPE(18:0), LPE(20:4), LPE(20:1), LPE(20:0)], lysophosphatidylcholine LPC(20:4) and lysophosphatidylserine LPS(19:0), as well as increase of sphingomyelin SM(36:2), in the plasma samples of pulmonary arterial hypertensive patients in comparison to the control group. Besides, their function as components of the biological membranes, these metabolites are also involved in the intracellular signaling pathways that are related to cell proliferation and apoptosis.CONCLUSIONS: The results obtained during this study confirm the potential of untargeted metabolomics to identify the molecular characteristics of the pathophysiology of atherosclerosis. The clinical relevance of this study constitutes the selection of a metabolic panel that can potentially detect and properly diagnose the disease.

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TWIST1 drives endothelial-to-mesenchymal-transition to stabilize atherosclerotic plaques [single cell RNA-seq]

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