Plasma ceramides are associated with outcomes in acute ischemic stroke patients

Lee, Tsung-Heng; Cheng, C. H.; Chao, Hsi‐Chun; Lee, Ching-Hua; Kuo, Ching‐Hua; Tang, Sung‐Chun; Jeng, Jiann‐Shing

doi:10.1016/j.jfma.2021.01.006

Cited by 20 publications

(19 citation statements)

References 44 publications

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“…Studies in tMCAO models have shown that there is an increase in levels of long and very-long-chain Cer in plasma following reperfusion ( Yang Y. et al, 2018 ; Chao et al, 2019 ). In fact, recent studies have described similar results in patients after a stroke ( Gui et al, 2020 ; Lee et al, 2021 ).…”

Section: Stroke and Ceramide Metabolismsupporting

confidence: 59%

“…Moreover, sphingolipidomics also showed its ability to study sphingolipids as potential biomarkers associated with neurodegenerative processes ( Ayub et al, 2021 ), demonstrating the involvement of sphingolipids in their underlying molecular mechanisms. Specifically, recent works on cerebral ischemia showed an alteration of the sphingolipid profile, both in pre-clinical ( Chao et al, 2019 ) and clinical studies ( Sun et al, 2017 ; Gui et al, 2020 ; Lee et al, 2021 ). Sun and others detected elevated levels of sphinganine and some phospholipids in serum samples ( Sun et al, 2017 ).…”

Section: Introductionmentioning

confidence: 99%

“…In addition, intracellular accumulation of Cer has been observed to be critical to induce neurodegeneration ( Jana et al, 2009 ). Different studies have observed the relationship between the metabolism of Cer and the progression of cerebral ischemia, in both in vitro hypoxic experiments and in preclinical or clinical studies ( Kang et al, 2010 ; Chao et al, 2019 ; Yusuf et al, 2019 ; Gui et al, 2020 ; Xia et al, 2020 ; Lee et al, 2021 ). Increased ceramide levels have been associated with reperfusion after an ischemic event ( Yusuf et al, 2019 ).…”

Section: Introductionmentioning

confidence: 99%

“…Later, Lee et al, also demonstrated the viability of Cer as a blood biomarker for the progression of patients after a stroke showing that control patients had higher levels of sphingosine 1-phosphate and very-long-chain Cer than patients with ischemic stroke. However, they reported an increase in long-chain Cer levels in ischemic stroke patients in correlation with the severity of the disease ( Lee et al, 2021 ). The reduction of S1P levels was also observed in acute ischemic stroke patients compared with healthy subjects ( Liu et al, 2020 ).…”

Section: Introductionmentioning

confidence: 99%

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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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Section: Stroke and Ceramide Metabolismsupporting

confidence: 59%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Involvement of Ceramide Metabolism in Cerebral Ischemia

Ouro

Correa-Paz²,

Maqueda³

et al. 2022

Front. Mol. Biosci.

View full text Add to dashboard Cite

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“…Previous evidence indicates that levels of ceramide are increased in pre-clinical models of stroke as well as in human patients [25][26][27].…”

Section: Expression Of Ceramide Synthases Is Defective In Multiple Tissues From Shrsp and Shrsr Modelsmentioning

confidence: 99%

Differential Expression of Sphingolipid Metabolizing Enzymes in Spontaneously Hypertensive Rats: A Possible Substrate for Susceptibility to Brain and Kidney Damage

Pepe

Cotugno

Marracino

et al. 2021

IJMS

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Alterations in the metabolism of sphingolipids, a class of biologically active molecules in cell membranes with direct effect on vascular homeostasis, are increasingly recognized as important determinant in different vascular disorders. However, it is not clear whether sphingolipids are implicated in the pathogenesis of hypertension-related cerebrovascular and renal damage. In this study, we evaluated the existence of possible abnormalities related to the sphingolipid metabolism in the brain and kidneys of two well validated spontaneously hypertensive rat strains, the stroke-prone (SHRSP) and the stroke-resistant (SHRSR) models, as compared to the normotensive Wistar Kyoto (WKY) rat strain. Our results showed a global alteration in the metabolism of sphingolipids in both cerebral and renal tissues of both hypertensive strains as compared to the normotensive rat. However, few defects, such as reduced expression of enzymes involved in the metabolism/catabolism of sphingosine-1-phosphate and in the de novo biosynthetic pathways, were exclusively detected in the SHRSP. Although further studies are necessary to fully understand the significance of these findings, they suggest that defects in specific lipid molecules and/or their related metabolic pathways may likely contribute to the pathogenesis of hypertensive target organ damage and may eventually serve as future therapeutic targets to reduce the vascular consequences of hypertension.

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Identification of a potential prognostic plasma biomarker of acute ischemic stroke via untargeted LC‐MS metabolomics

Lin

Chen

2023

Proteomics Clinical Apps

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PurposeStroke is the sudden death of brain cells in a localized area due to an inadequate blood flow or blood vessel rupture, and it seriously affects the quality of life. The metabolite biomarkers are needed for predicting the functional outcome of acute ischemic stroke (AIS).Experimental DesignTo identify biomarkers for AIS, untargeted LC/MS metabolomics was performed on plasma samples from subjects with favorable prognosis (mRS ≤ 2) and unfavorable prognosis (mRS > 2). The identified markers were further absolutely quantified by a targeted MRM approach.ResultsThere were 10 upregulated and 26 downregulated markers. Among these candidates, one was successfully identified as glycocholic acid and then absolutely quantified in plasma samples. Glycocholic acid could discriminate between subjects with favorable and unfavorable prognosis with an area under the curve (AUC) of 0.68 and odds ratio of 5.88.Conclusions and Clinical RelevanceGlycocholic acid was identified as a potential plasma metabolite marker of non‐progressive outcomes after ischemic stroke and could serve as predictive prognostic markers for clinical acute stroke outcomes.

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Plasma ceramides are associated with outcomes in acute ischemic stroke patients

Cited by 20 publications

References 44 publications

Involvement of Ceramide Metabolism in Cerebral Ischemia

Involvement of Ceramide Metabolism in Cerebral Ischemia

Differential Expression of Sphingolipid Metabolizing Enzymes in Spontaneously Hypertensive Rats: A Possible Substrate for Susceptibility to Brain and Kidney Damage

Identification of a potential prognostic plasma biomarker of acute ischemic stroke via untargeted LC‐MS metabolomics

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