A metabolomic study on high-risk stroke patients determines low levels of serum lysine metabolites: a retrospective cohort study

Abstract

Identifying changes in serum metabolites during cerebral ischemia is an important approach for early diagnosis of thrombotic stroke. Herein, we highlight novel biomarkers for early diagnosis of patients at high risk of thrombotic stroke using high resolution metabolomics (HRM). In this retrospective cohort study, serum samples obtained from patients at risk of thrombotic stroke (n = 62) and non-risk individuals (n = 348) were tested using HRM, coupled with LC-MS/MS, to discriminate between metabolic profiles of control and stroke risk patients. Multivariate analysis and orthogonal partial least square-discriminant analysis (OPLS-DA) were performed to determine the top 5% metabolites within 95% group identities, followed by filtering with p-value <0.05 and annotating significant metabolites using a Metlin database. Mapping identified features from Kyoto Encyclopedia of Genes and Genomes (KEGG) and Mummichog resulted in 341 significant features based on OPLS-DA with p-value <0.05. Among these 341 features, nine discriminated the thrombotic stroke risk group from the control group: low levels of N-acetyl-l-lysine, 5-aminopentanoate, cadaverine, 2-oxoglutarate, nicotinamide, l-valine, S-(2-methylpropionyl)-dihydrolipoamide-E and ubiquinone, and elevated levels of homocysteine sulfinic acid. Further analysis showed that these metabolite biomarkers are specifically related to stroke occurrence, and unrelated to other factors such as diabetes or smoking. Lower levels of lysine catabolites in thrombotic stroke risk patients, as compared to the control, supports targeting these compounds as novel biomarkers for early and non-invasive detection of a thrombotic stroke.

Identification of potential biomarkers in cholestasis and the therapeutic effect of melatonin by metabolomics, multivariate data and pathway analyses

“…Additionally, 5-aminopentanoate has been reported to serve an important role in proline metabolism and may participate in lysine degradation in Phaeobacter inhibens DSM 17395 ( 46 ). Lee et al ( 47 ) also found that lysine degradation is specifically associated with stroke occurrence, and that low expression of 5-aminopentanoate may increase the risk of thrombotic stroke. In the present study, serum GSH, 5-methoxytryptamine, indolepropionic and 5-aminopen-tanoate levels were decreased in cholestasis model rats when compared with the control rats; however, these level were increased by MT treatment.…”

Circular RNA expression profile in blood according to ischemic stroke etiology

“…A recent study among hypertensive subjects revealed altered metabolic pathways, including lysine degradation, related to incident ischemic stroke [46]. Moreover, a metabolomic study showed that levels of serum lysine catabolites were low in patients at high-risk of suffering ischemic stroke [47].…”

Circulating Metabolites as Potential Biomarkers for Neurological Disorders—Metabolites in Neurological Disorders

“…Furthermore, the downregulation of some metabolites, such as L-homoarginine, cadaverine, 2-oxoglutarate, nicotinamide, valine, and ubiquinone, has also been associated with an increased risk of stroke [ 164 , 165 , 166 ]. Homoarginine has been described as part of nitric oxide metabolism and can regulate blood flow and pressure, cell viability, insulin secretion, and platelet aggregation [ 164 ].…”

“…A few studies have shown that a decrease in homoarginine levels can be associated with increased stroke mortality [ 164 , 166 ]. In addition, the reduction of lysine catabolites has been associated with poor stroke outcomes [ 165 ].…”