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Comparative lipid profiling of murine and human atherosclerotic plaques using high-resolution MALDI MSI.

ABSTRACT: The distribution of atherosclerotic lesions in the aorta and its branches of ApoE knockout (ApoE^-/-) mice is like that of patients with atherosclerosis. By using high-resolution MALDI mass spectrometry imaging (MSI), we aimed at characterizing universally applicable physiological biomarkers by comparing the murine lipid marker profile with that of human atherosclerotic arteries. Therefore, the aorta or carotid artery of male ApoE^-/- mice at different ages, human arteries with documented atherosclerotic changes originated from amputated limbs, and corresponding controls were analysed. Obtained data were subjected to multivariate statistical analysis to identify potential biomarkers. Thirty-one m/z values corresponding to individual lipid species of cholesterol esters, lysophosphatidylcholines, lysophosphatidylethanolamines, and cholesterol derivatives were found to be specific in aortic atherosclerotic plaques of old ApoE^-/- mice. The lipid composition at related vessel positions of young ApoE^-/- mice was more comparable with wild-type mice. Twenty-six m/z values of the murine lipid markers were found in human atherosclerotic peripheral arteries but also control vessels and showed a more patient-dependent diverse distribution. Extensive data analysis without marker preselection based on mouse data revealed lysophosphatidylcholine and glucosylated cholesterol species, the latter not being detected in the murine atherosclerotic tissue, as specific potential novel human atherosclerotic vessel markers. Despite the heterogeneous lipid profile of atherosclerotic peripheral arteries derived from human patients, we identified lipids specifically colocalized to atherosclerotic human tissue and plaques in ApoE^-/- mice. These data highlight species-dependent differences in lipid profiles between peripheral artery disease and aortic atherosclerosis.

SUBMITTER: Khamehgir-Silz P

PROVIDER: S-EPMC8766400 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:Background and purposeIntracranial atherosclerosis is one of the main causes of stroke, and high-resolution magnetic resonance imaging provides useful imaging biomarkers related to the risk of ischemic events. This study aims to evaluate differences in histogram features between culprit and nonculprit intracranial atherosclerosis using high-resolution magnetic resonance imaging.MethodsTwo hundred forty-seven patients with intracranial atherosclerosis who underwent high-resolution magnetic resonance imaging sequentially between January 2015 and December 2016 were recruited. Quantitative features, including stenosis, plaque burden, minimum luminal area, intraplaque hemorrhage, enhancement ratio, and dispersion of signal intensity (coefficient of variation), were analyzed based on T2-, T1-, and contrast-enhanced T1-weighted images. Step-wise regression analysis was used to identify key determinates differentiating culprit and nonculprit plaques and to calculate the odds ratios (ORs) with 95% CIs.ResultsIn total, 190 plaques were identified, of which 88 plaques (37 culprit and 51 nonculprit) were located in the middle cerebral artery and 102 (57 culprit and 45 nonculprit) in the basilar artery. Nearly 90% of culprit lesions had a degree of luminal stenosis of <70%. Multiple logistic regression analyses showed that intraplaque hemorrhage (OR, 16.294 [95% CI, 1.043-254.632]; P=0.047), minimum luminal area (OR, 1.468 [95% CI, 1.032-2.087]; P=0.033), and coefficient of variation (OR, 13.425 [95% CI, 3.987-45.204]; P<0.001) were 3 significant features in defining culprit plaques in middle cerebral artery. The enhancement ratio (OR, 9.476 [95% CI, 1.256-71.464]; P=0.029), intraplaque hemorrhage (OR, 2.847 [95% CI, 0.971-10.203]; P=0.046), and coefficient of variation (OR, 10.068 [95% CI, 2.820-21.343]; P<0.001) were significantly associated with plaque type in basilar artery. Coefficient of variation was a strong independent predictor in defining plaque type for both middle cerebral artery and basilar artery with sensitivity, specificity, and accuracy being 0.79, 0.80, and 0.80, respectively.ConclusionsFeatures characterized by high-resolution magnetic resonance imaging provided complementary values over luminal stenosis in defined lesion type for intracranial atherosclerosis; the dispersion of signal intensity in histogram analysis was a particularly effective predictive parameter.

Project description:Atherosclerosis is a chronic inflammatory disease with high prevalence and mortality. The rupture of atherosclerotic plaque is the main reason for the clinical events caused by atherosclerosis. Making clear the transcriptomic and proteomic profiles between the stabe and unstable atherosclerotic plaques is crucial to prevent the clinical manifestations. In the present study, 5 stable and 5 unstable human carotid atherosclerotic plaques were obtained by carotid endarterectomy. The samples were used for the whole transcriptome sequencing (RNA-Seq) by the Next-Generation Sequencing using the Illumina HiSeq, and for proteome analysis by HPLC-MS/MS. The lncRNA-targeted genes and circRNA-originated genes were identified by analyzing their location and sequence. Gene Ontology and KEGG enrichment was carried out to analyze the functions of differentially expressed RNAs and proteins. The protein-protein interactions (PPI) network was constructed by the online tool STRING. The consistency of transcriptome and proteome were analyzed, and the lncRNA/circRNA-miRNA-mRNA interactions were predicted. As a result, 202 mRNAs, 488 lncRNAs, 91 circRNAs, and 293 proteins were identified to be differentially expressed between stable and unstable atherosclerotic plaques. The 488 lncRNAs might target 381 protein-coding genes by cis-acting mechanisms. Sequence analysis indicated the 91 differentially expressed circRNAs were originated from 97 protein-coding genes. These differentially expressed RNAs and proteins were mainly enriched in the terms of the cellular response to stress or stimulus, the regulation of gene transcription, the immune response, the nervous system functions, the hematologic activities, and the endocrine system. These results were consistent with the previous reported data in the dataset GSE41571. Further analysis identified CD5L, S100A12, CKB (target gene of lncRNA MSTRG.11455.17), CEMIP (target gene of lncRNA MSTRG.12845), and SH3GLB1 (originated gene of hsacirc_000411) to be critical genes in regulating the stability of atherosclerotic plaques. Our results provided a comprehensive transcriptomic and proteomic knowledge on the stability of atherosclerotic plaques.

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Comparative lipid profiling of murine and human atherosclerotic plaques using high-resolution MALDI MSI.

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