Plasma lipidomic analysis of sphingolipids in patients with large artery atherosclerosis cerebrovascular disease and cerebral small vessel disease

You, Qian; Peng, Qing; Yu, Zemou; Jin, Haiqiang; Zhang, Jing; Sun, Wei; Huang, Yining

doi:10.1042/bsr20201519

Cited by 21 publications

(17 citation statements)

References 43 publications

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“…Previous metabolomics studies have shown associations of lower levels of ceramide ratios with fewer number of cerebral microbleeds 20 and increased risk of incident dementia, 21 and another study showed associations of ceramides and sphingomyelins with SVD. 22 In the present study, lower levels of serum sphingomyelins and ceramides were associated with lower MDNPH, higher WMH volume and PSMD, increased number of lacunes, greater brain atrophy and impaired cognition in baseline analyses even after further adjustment. Only one sphingomyelin had a statistically significant association with executive function when assessing the annualized change in metabolite levels, suggesting that the absolute levels of the metabolites at baseline are more relevant in evaluating their effects on SVD and cognition than how those levels change over time.…”

Section: Discussionsupporting

confidence: 47%

Metabolomic profiling in small vessel disease identifies multiple associations with disease severity

Harshfield

Sands

Tuladhar

et al. 2022

Brain

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Cerebral small vessel disease is a major cause of vascular cognitive impairment and dementia. There are few treatments, largely reflecting limited understanding of the underlying pathophysiology. Metabolomics can be used to identify novel risk factors in order to better understand pathogenesis and to predict disease progression and severity. We analysed data from 624 patients with symptomatic cerebral small vessel disease from two prospective cohort studies. Serum samples were collected at baseline and patients underwent MRI scans and cognitive testing at regular intervals with up to 14 years of follow-up. Using ultra-performance liquid chromatography mass spectrometry and nuclear magnetic resonance spectroscopy, we obtained metabolic and lipidomic profiles from 369 annotated metabolites and 54,764 unannotated features and examined their association with respect to disease severity, assessed using MRI small vessel disease markers, cognition, and future risk of all-cause dementia. Our analysis identified 28 metabolites that were significantly associated with small vessel disease imaging markers and cognition. Decreased levels of multiple glycerophospholipids and sphingolipids were associated with increased small vessel disease load as evidenced by higher white matter hyperintensities volume, lower mean diffusivity normalised peak height, greater brain atrophy, and impaired cognition. Higher levels of creatine, FA(18:2(OH)), and SM(d18:2/24:1) were associated with increased lacune count, higher white matter hyperintensities volume, and impaired cognition. Lower baseline levels of carnitines and creatinine were associated with higher annualised change in peak width of skeletonised mean diffusivity, and 25 metabolites, including lipoprotein subclasses, amino acids, and xenobiotics, were associated with future dementia incidence. Our results show multiple distinct metabolic signatures that are associated with imaging markers of small vessel disease, cognition, and conversion to dementia. Further research should assess causality and the use of metabolomic screening to improve the ability to predict future disease severity and dementia risk in small vessel disease. The metabolomic profiles may also provide novel insights into disease pathogenesis and help identify novel treatment approaches.

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Section: Discussionsupporting

confidence: 47%

Metabolomic profiling in small vessel disease identifies multiple associations with disease severity

Harshfield

Sands

Tuladhar

et al. 2022

Brain

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“…Furthermore, high levels of long-chain Cer have been associated with BBB disruption ( Vutukuri et al, 2018 ; Bekhite et al, 2021 ). Moreover, elevated plasma levels of Cer were recently observed from stroke patients with large artery atherosclerosis, and cerebral small vessel disease ( You et al, 2020 ).…”

Section: Introductionmentioning

confidence: 99%

Involvement of Ceramide Metabolism in Cerebral Ischemia

Ouro

Correa-Paz²,

Maqueda³

et al. 2022

Front. Mol. Biosci.

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Ischemic stroke, caused by the interruption of blood flow to the brain and subsequent neuronal death, represents one of the main causes of disability in worldwide. Although reperfusion therapies have shown efficacy in a limited number of patients with acute ischemic stroke, neuroprotective drugs and recovery strategies have been widely assessed, but none of them have been successful in clinical practice. Therefore, the search for new therapeutic approaches is still necessary. Sphingolipids consist of a family of lipidic molecules with both structural and cell signaling functions. Regulation of sphingolipid metabolism is crucial for cell fate and homeostasis in the body. Different works have emphasized the implication of its metabolism in different pathologies, such as diabetes, cancer, neurodegeneration, or atherosclerosis. Other studies have shown its implication in the risk of suffering a stroke and its progression. This review will highlight the implications of sphingolipid metabolism enzymes in acute ischemic stroke.

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“…ACC1, mainly acting on the fatty acid synthesis and fatty acid oxidation, is observed to involve in metabolic syndrome (including atherogenic dyslipidemia, diabetes, and hypertension), which is a clustering of cardiovascular/cerebrovascular risk factors. [21][22][23][24] For instance, one previous study shows that the overexpression of ACC1 facilitates lipid accumulation in macrophage foam cells and further aggravates atherosclerosis in apolipoprotein E-deficient mice. 25 Also, another study finds that ACC1 expression is elevated in atherosclerotic mice.…”

Section: Discussionmentioning

confidence: 99%

Correlation of acetyl‐coenzyme A carboxylase 1 with Th17 and Th1 cells, serving as a potential prognostic biomarker for acute ischemic stroke patients

Jiang

Meng

et al. 2022

Clinical Laboratory Analysis

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Background Acetyl‐coenzyme A carboxylase 1 (ACC1) regulates lipid homeostasis, T helper (Th) cell differentiation, oxidative stress, inflammation response, and neurological process, engaging in acute ischemic stroke (AIS) pathogenesis, while its clinical utility in AIS is unclear. Hence, this study intended to explore the correlation among blood ACC1, Th17, and Th1 cells, and ACC1’s potency as a prognostic biomarker for AIS management. Methods ACC1 in peripheral blood mononuclear cells (PBMCs) of 160 AIS patients and 30 controls were determined using RT‐qPCR; blood Th17 and Th1 cells in AIS patients were quantified by flow cytometry. Results ACC1 was increased in AIS patients compared with controls (median (interquartile range): 2.540 (1.753–3.548) vs. 0.980 (0.655–1.743), p < 0.001), which exhibited a good value to reflect AIS risk with the area under the curve of 0.872 (95% CI: 0.805–0.939). Moreover, ACC1 was positively linked with Th17 (r = 0.374, p < 0.001) and Th1 (r = 0.178, p = 0.024) cells in AIS patients. Additionally, ACC1 (r = 0.328, p < 0.001), Th17 (r = 0.272, p = 0.001), and Th1 cells (r = 0.195, p = 0.014) were positively associated with the National Institutes of Health Stroke Scale score in AIS patients. ACC1 high vs. low (p = 0.038) and Th17 high vs. low (p = 0.026) were related to shortened recurrence‐free survival (RFS) in AIS patients, while Th1 cells (p = 0.179) were not correlated with RFS. Whereas ACC1 (p = 0.248), Th17 (p = 0.079), and Th1 cells (p = 0.130) were not linked with overall survival (OS) in AIS patients. Conclusion Circulating ACC1 overexpression correlates with increased Th17, Th1 cells, NIHSS score, and shortened RFS in AIS patients.

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Plasma lipidomic analysis of sphingolipids in patients with large artery atherosclerosis cerebrovascular disease and cerebral small vessel disease

Cited by 21 publications

References 43 publications

Metabolomic profiling in small vessel disease identifies multiple associations with disease severity

Metabolomic profiling in small vessel disease identifies multiple associations with disease severity

Involvement of Ceramide Metabolism in Cerebral Ischemia

Correlation of acetyl‐coenzyme A carboxylase 1 with Th17 and Th1 cells, serving as a potential prognostic biomarker for acute ischemic stroke patients

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