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Discovery of potential biomarkers for human atherosclerotic abdominal aortic aneurysm through untargeted metabolomics and transcriptomics.

ABSTRACT: Abdominal aortic aneurysm (AAA) and atherosclerosis (AS) have considerable similarities in clinical risk factors and molecular pathogenesis. The aim of our study was to investigate the differences between AAA and AS from the perspective of metabolomics, and to explore the potential mechanisms of differential metabolites via integration analysis with transcriptomics. Plasma samples from 32 AAA and 32 AS patients were applied to characterize the metabolite profiles using untargeted liquid chromatography-mass spectrometry (LC-MS). A total of 18 remarkably different metabolites were identified, and a combination of seven metabolites could potentially serve as a biomarker to distinguish AAA and AS, with an area under the curve (AUC) of 0.93. Subsequently, we analyzed both the metabolomics and transcriptomics data and found that seven metabolites, especially 2'-deoxy-D-ribose (2dDR), were significantly correlated with differentially expressed genes. In conclusion, our study presents a comprehensive landscape of plasma metabolites in AAA and AS patients, and provides a research direction for pathogenetic mechanisms in atherosclerotic AAA.

SUBMITTER: Ji L

PROVIDER: S-EPMC8435341 | biostudies-literature | 2021 Sept 15

REPOSITORIES: biostudies-literature

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Discovery of potential biomarkers for human atherosclerotic abdominal aortic aneurysm through untargeted metabolomics and transcriptomics.

Ji Lei L Chen Siliang S Gu Guangchao G Wang Wei W Ren Jinrui J Xu Fang F Li Fangda F Wu Jianqiang J Yang Dan D Zheng Yuehong Y

Journal of Zhejiang University. Science. B 20210901 9

Abdominal aortic aneurysm (AAA) and atherosclerosis (AS) have considerable similarities in clinical risk factors and molecular pathogenesis. The aim of our study was to investigate the differences between AAA and AS from the perspective of metabolomics, and to explore the potential mechanisms of differential metabolites via integration analysis with transcriptomics. Plasma samples from 32 AAA and 32 AS patients were applied to characterize the metabolite profiles using untargeted liquid chromato ...[more]

PMID: 34514753

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Project description:ImportancePatients with abdominal aortic aneurysm have a high risk of ischemic events associated with concomitant atherosclerotic cardiovascular disease, and current clinical practice guidelines recommend antiplatelet therapy to mitigate this risk. However, in patients with aneurysms without symptomatic atherosclerosis, the benefit of antiplatelet therapy has been sparsely investigated.ObjectiveTo estimate the effect of antiplatelets on the risk of ischemic events and bleeding in individuals with abdominal aneurysms with no symptomatic atherosclerotic vascular disease.Design, setting, and participantsA comparative effectiveness research study using a target trial emulation framework was performed. Population-based, cross-linked observational data from Danish national health registries containing comprehensive, individual-level information on all Danish citizens were used to evaluate patients who were antiplatelet-naive and diagnosed with abdominal aortic aneurysms, with no record of symptomatic atherosclerotic vascular disease, from January 1, 2010, through August 21, 2021.ExposurePrescription filled for aspirin or clopidogrel.Main outcomes and measuresRisk of ischemic events (myocardial infarction and/or ischemic stroke) and risk of major bleeding. For target trial emulation, trials were emulated as sequential, contingent on patient eligibility at the time of inclusion, and were evaluated by means of pooled logistic regression models to estimate the intention-to-treat and as-treated effects, expressed as hazard ratio (HR) and event-free survival.ResultsA total of 6344 patients (65.2% men; age, 72 [IQR, 64-78] years) provided 131 047 trial cases; 3363 of these cases involved initiation of antiplatelet therapy and 127 684 did not. A total of 182 ischemic events occurred among initiators and 5602 ischemic events occurred among noninitiators, corresponding to an intention-to-treat HR of 0.91 (95% CI, 0.73-1.17) and an estimated absolute event-free survival difference of -0.6% (95% CI, -1.7% to 0.5%). After censoring nonadherent person-time, the treatment HR was 0.90 (95% CI, 0.68-1.20), with similar risk difference. For bleeding, the intention-to-treat HR was 1.26 (95% CI, 0.97-1.58) and the event-free survival difference was 1.0%. The treatment HR was 1.21 (95% CI, 0.82-1.72); the risk difference was similar.Conclusions and relevanceIn this study, no evidence of effectiveness of antiplatelet therapy to lower the risk of ischemic events and a trend toward higher bleeding risk was noted. The observed differences between the treatment groups were minimal, suggesting limited clinical relevance of antiplatelet treatment.

Dataset Information

Discovery of potential biomarkers for human atherosclerotic abdominal aortic aneurysm through untargeted metabolomics and transcriptomics.

Publications

Discovery of potential biomarkers for human atherosclerotic abdominal aortic aneurysm through untargeted metabolomics and transcriptomics.

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