Global Metabolomic Profiling Reveals Disrupted Lipid and Amino Acid Metabolism Between the Acute and Chronic Stages of Ischemic Stroke

Sidorov, Evgeny G.; Xu, Chao; Garcia-Ramiu, Jonathan; Apple, Blair; García, Jorge; Gordon, David; Chainakul, Juliane; Sanghera, Dharambir K.

doi:10.1016/j.jstrokecerebrovasdis.2022.106320

Cited by 11 publications

(5 citation statements)

References 28 publications

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“…HT intake also decreased the expression of HSL, an enzyme abundant in adipose tissue that hydrolyzes diacylglycerols, generating monoacylglycerols and fatty acids. A recent metabolomic analysis carried out in serum revealed a consistent increase of mono/diacylglycerols and medium/long-chain fatty acids in the acute phase of ischemic stroke [39], suggesting an increased activation of this enzyme. HSL also has a cholesteryl-ester hydrolase activity, and its expression in macrophages favors cholesterol efflux from foam cells.…”

Section: Discussionmentioning

confidence: 95%

Hydroxytyrosol, a Promising Supplement in the Management of Human Stroke: An Exploratory Study

Naranjo,

Álvarez-Soria,

Aranda-Villalobos

et al. 2024

IJMS

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Hydroxytyrosol (HT) is a bioactive olive oil phenol with beneficial effects in a number of pathological situations. We have previously demonstrated that an HT-enriched diet could serve as a beneficial therapeutic approach to attenuate ischemic-stroke-associated damage in mice. Our exploratory pilot study examined this effect in humans. Particularly, a nutritional supplement containing 15 mg of HT/day was administered to patients 24 h after the onset of stroke, for 45 days. Biochemical and oxidative-stress-related parameters, blood pressure levels, serum proteome, and neurological and functional outcomes were evaluated at 45 and 90 days and compared to a control group. The main findings were that the daily administration of HT after stroke could: (i) favor the decrease in the percentage of glycated hemoglobin and diastolic blood pressure, (ii) control the increase in nitric oxide and exert a plausible protective effect in oxidative stress, (iii) modulate the evolution of the serum proteome and, particularly, the expression of apolipoproteins, and (iv) be beneficial for certain neurological and functional outcomes. Although a larger trial is necessary, this study suggests that HT could be a beneficial nutritional complement in the management of human stroke.

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Section: Discussionmentioning

confidence: 95%

Hydroxytyrosol, a Promising Supplement in the Management of Human Stroke: An Exploratory Study

Naranjo,

Álvarez-Soria,

Aranda-Villalobos

et al. 2024

IJMS

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“…Moreover, sphingolipids are an important structural component of cell membranes, which plays an essential role in controlling the signal transduction of cell proliferation, differentiation, and apoptosis [ 42 ]. Moreover, there is a connection and/or cascade reaction among tyrosine metabolism, sphingolipid metabolism, serotonergic synapses, pathways of multiple neurodegeneration diseases, and GABAergic synapses [ 43 , 44 ]. It is also applicable to our metabolism results from serum exosomes of RIPC participants.…”

Section: Discussionmentioning

confidence: 99%

Identification of serum exosomal metabolomic and proteomic profiles for remote ischemic preconditioning

Qiu

Chen

et al. 2023

J Transl Med

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Background Remote ischemic preconditioning (RIPC) refers to a brief episode of exposure to potential adverse stimulation and prevents injury during subsequent exposure. RIPC has been shown to increase tolerance to ischemic injury and improve cerebral perfusion status. Exosomes have a variety of activities, such as remodeling the extracellular matrix and transmitting signals to other cells. This study aimed to investigate the potential molecular mechanism of RIPC-mediated neuroprotection. Methods Sixty adult male military personnel participants were divided into the control group (n = 30) and the RIPC group (n = 30). We analyzed the differential metabolites and proteins in the serum exosomes of RIPC participants and control subjects. Results Eighty-seven differentially expressed serum exosomal metabolites were found between the RIPC and control groups, which were enriched in pathways related to tyrosine metabolism, sphingolipid metabolism, serotonergic synapses, and multiple neurodegeneration diseases. In addition, there were 75 differentially expressed exosomal proteins between RIPC participants and controls, which involved the regulation of insulin-like growth factor (IGF) transport, neutrophil degranulation, vesicle-mediated transport, etc. Furthermore, we found differentially expressed theobromine, cyclo gly-pro, hemopexin (HPX), and apolipoprotein A1 (ApoA1), which are associated with neuroprotective benefits in ischemia/reperfusion injury. In addition, five potential metabolite biomarkers, including ethyl salicylate, ethionamide, piperic acid, 2, 6-di-tert-butyl-4-hydroxymethylphenol and zerumbone, that separated RIPC from control individuals were identified. Conclusion Our data suggest that serum exosomal metabolites are promising biomarkers for RIPC, and our results provide a rich dataset and framework for future analyses of cerebral ischemia‒reperfusion injury under ischemia/reperfusion conditions.

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“…Similar findings were reported by another study from Sidorov et al, which evaluated a broader range of metabolites. Consistent increases in mono/diacylglycerol, sphingolipid, and specific amino acid metabolites (glycine, valine, and tyrosine) were observed in the acute phase, while fatty acid, phospholipid, and other amino acid (alanine, aspartic acid, tyramine) levels decreased [ 45 ]. Although a control group was absent in this study, these findings suggest potential metabolic markers for the acute phase.…”

Section: Metabolomics Research In Ismentioning

confidence: 99%

Metabolomic discoveries for early diagnosis and traditional Chinese medicine efficacy in ischemic stroke

Wei,

Chen,

Deng

et al. 2024

Biomark Res

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Ischemic stroke (IS), a devastating cerebrovascular accident, presents with high mortality and morbidity. Following IS onset, a cascade of pathological changes, including excitotoxicity, inflammatory damage, and blood-brain barrier disruption, significantly impacts prognosis. However, current clinical practices struggle with early diagnosis and identifying these alterations. Metabolomics, a powerful tool in systems biology, offers a promising avenue for uncovering early diagnostic biomarkers for IS. By analyzing dynamic metabolic profiles, metabolomics can not only aid in identifying early IS biomarkers but also evaluate Traditional Chinese Medicine (TCM) efficacy and explore its mechanisms of action in IS treatment. Animal studies demonstrate that TCM interventions modulate specific metabolite levels, potentially reflecting their therapeutic effects. Identifying relevant metabolites in cerebral ischemia patients holds immense potential for early diagnosis and improved outcomes. This review focuses on recent metabolomic discoveries of potential early diagnostic biomarkers for IS. We explore variations in metabolites observed across different ages, genders, disease severity, and stages. Additionally, the review examines how specific TCM extracts influence IS development through metabolic changes, potentially revealing their mechanisms of action. Finally, we emphasize the importance of integrating metabolomics with other omics approaches for a comprehensive understanding of IS pathophysiology and TCM efficacy, paving the way for precision medicine in IS management.

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Global Metabolomic Profiling Reveals Disrupted Lipid and Amino Acid Metabolism Between the Acute and Chronic Stages of Ischemic Stroke

Cited by 11 publications

References 28 publications

Hydroxytyrosol, a Promising Supplement in the Management of Human Stroke: An Exploratory Study

Hydroxytyrosol, a Promising Supplement in the Management of Human Stroke: An Exploratory Study

Identification of serum exosomal metabolomic and proteomic profiles for remote ischemic preconditioning

Metabolomic discoveries for early diagnosis and traditional Chinese medicine efficacy in ischemic stroke

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