Identification of essential hypertension biomarkers in human urine by non-targeted metabolomics based on UPLC-Q-TOF/MS

Zhao, Huan; Liu, Yijia; Zhu, Li; Yan-qi, Song; Cai, Xuemeng; Liu, Yuechen; Zhang, Tianpu; Liu, Yang; Li, Lin; Gao, Shan; Li, Yubo; Yu, Chunquan

doi:10.1016/j.cca.2018.08.006

Cited by 44 publications

(52 citation statements)

References 37 publications

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“…Oxidative stress is known to be involved in the pathogenesis of CVD [ 23 – 25 ], and prior metabolomics studies in human urine point to an important contribution for oxidative stress in acute coronary syndrome [ 26 ] and hypertension in persons < 50 years [ 27 ]. In the same line, our previous proteomic study highlighted oxidative stress as a major functional category that is altered by cardiovascular risk factors already present in young adults [ 20 ].…”

Section: Discussionmentioning

confidence: 99%

Urinary metabolic signatures reflect cardiovascular risk in the young, middle-aged, and elderly populations

et al. 2020

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The predictive value of traditional cardiovascular risk estimators is limited, and young and elderly populations are particularly underrepresented. We aimed to investigate the urine metabolome and its association with cardiovascular risk to identify novel markers that might complement current estimators based on age. Urine samples were collected from 234 subjects categorized into three age-grouped cohorts: 30–50 years (cohort I, young), 50–70 years (cohort II, middle-aged), and > 70 years (cohort III, elderly). Each cohort was further classified into three groups: (a) control, (b) individuals with cardiovascular risk factors, and (c) those who had a previous cardiovascular event. Novel urinary metabolites linked to cardiovascular risk were identified by nuclear magnetic resonance in cohort I and then evaluated by target mass spectrometry quantification in all cohorts. A previously identified metabolic fingerprint associated with atherosclerosis was also analyzed and its potential risk estimation investigated in the three aged cohorts. Three different metabolic signatures were identified according to age: 2-hydroxybutyrate, gamma-aminobutyric acid, hypoxanthine, guanidoacetate, oxaloacetate, and serine in young adults; citrate, cyclohexanol, glutamine, lysine, pantothenate, pipecolate, threonine, and tyramine shared by middle-aged and elderly adults; and trimethylamine N-oxide and glucuronate associated with cardiovascular risk in all three cohorts. The urinary metabolome contains a metabolic signature of cardiovascular risk that differs across age groups. These signatures might serve to complement existing algorithms and improve the accuracy of cardiovascular risk prediction for personalized prevention. Key messages • Cardiovascular risk in the young and elderly is underestimated. • The urinary metabolome reflects cardiovascular risk across all age groups. • Six metabolites constitute a metabolic signature of cardiovascular risk in young adults. • Middle-aged and elderly adults share a cardiovascular risk metabolic signature. • TMAO and glucuronate levels reflect cardiovascular risk across all age groups.

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Section: Discussionmentioning

confidence: 99%

Urinary metabolic signatures reflect cardiovascular risk in the young, middle-aged, and elderly populations

et al. 2020

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“…Moreover, compared with hypertension patients, the metabolic pathways of SHRs to some extent show similarities. For instance, in the study of metabolomics on human hypertension, it found that the differential biomarkers are closely related to amino acid metabolism [58], and the study of young hypertensive men on metabolomics also indicate that variances of amino acids have a major impact on the metabolic change [59]. In addition, metabolites variability within a 24 h period has been closely associated with metabolic disorders [6,9].…”

Section: Discussionmentioning

confidence: 99%

Establishment of the circadian metabolic phenotype strategy in spontaneously hypertensive rats: a dynamic metabolomics study

Wang

et al. 2020

J Transl Med

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Background: Circadian rhythms play a fundamental role in the progression of cardiovascular events. Almost all cardiovascular diseases have a circadian misalignment usually characterized by changes in metabolites. This study aimed to dynamically monitor rhythmic biomarkers, to elucidate the metabolic pathways that are potentially under circadian control in spontaneously hypertensive rats (SHRs), and to eventually establish a circadian metabolic phenotype strategy based on metabolomics. Methods: In this study, an untargeted metabolomics technology was used to dynamically monitor changes in serum metabolites between SHR model group and WKY control group. Liquid chromatography-mass spectrometry (LC-MS) combined with multivariate statistical analysis was applied to identify markers of hypertension rhythm imbalance. The concentrations of amino acids and their metabolites identified as markers were quantified by a subsequent targeted metabolomics analysis. Overall, these approaches comprehensively explored the rhythm mechanism and established a circadian metabolic phenotype strategy. Results: The metabolic profile revealed a disorder in the diurnal metabolism pattern in SHRs. Moreover, multivariate statistical analysis revealed metabolic markers of rhythm homeostasis, such as arginine, proline, phenylalanine, citric acid, l-malic acid, succinic acid, etc., accompanied by an imbalance in hypertension. The key metabolic pathways related to rhythm imbalance in hypertension were found by enrichment analysis, including amino acid metabolism, and the tricarboxylic acid cycle (TCA). In addition, the quantitative analysis of amino acids and their metabolites showed that the changes in leucine, isoleucine, valine, taurine, serine, and glycine were the most obvious. Conclusions: In summary, this study illustrated the relationship between metabolites and the pathways across time on hypertension. These results may provide a theoretical basis for personalized treatment programmes and timing for hypertension.

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“…These studies have been recently reviewed 9,10 . The metabolomic signatures published to date showed a wide variety of quantitative metabolite traits related to arterial hypertension such as amino acids (alanine, serine, glycine, methionine, arginine, tyrosine and isoleucine), nucleotide bases (adenine and uracil), hormones (epiandrosterone sulfate, 5 α-androstan-3β-diol disulfate, androsterone sulfate, melatonin, cortolone, dihydroxyphenylglycol, and hydroxyandrosterone), organic acids (hippurate, pyruvate, hexadecanedioate, formate, methyl nicotinate, dicarboxylic acids, butyrate and fumarate, lactate, malate and pyruvate), and hexoses [11][12][13][14][15][16][17] . A variety of lipids were also reported to be quantitatively modified in hypertension, such as phosphatidylcholines, ceramides, phosphatidylinositols, diacylglycerols, and fatty acids 14,16,18,19 .…”

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confidence: 99%

“…The metabolomic signatures published to date showed a wide variety of quantitative metabolite traits related to arterial hypertension such as amino acids (alanine, serine, glycine, methionine, arginine, tyrosine and isoleucine), nucleotide bases (adenine and uracil), hormones (epiandrosterone sulfate, 5 α-androstan-3β-diol disulfate, androsterone sulfate, melatonin, cortolone, dihydroxyphenylglycol, and hydroxyandrosterone), organic acids (hippurate, pyruvate, hexadecanedioate, formate, methyl nicotinate, dicarboxylic acids, butyrate and fumarate, lactate, malate and pyruvate), and hexoses [11][12][13][14][15][16][17] . A variety of lipids were also reported to be quantitatively modified in hypertension, such as phosphatidylcholines, ceramides, phosphatidylinositols, diacylglycerols, and fatty acids 14,16,18,19 . Changes in these signatures under the influence of dietary interventions in hypertensive patients (proline-betaine, carnitine, hippurate, cresyl sulfate, phenylacetylglutamine, N-methyl-2-pyridone-5-carboxyamide, methionine sulfone, and β-hydroxyisovalerate) 20,21 or under various antihypertensive therapies (acylcarnitines, hexadecanedioate uric acid, lysophosphatidylcholines, triacylglycerols, and cholesterol esters) have also been reported [22][23][24] .…”

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confidence: 99%

Sexual Dimorphism of Metabolomic Profile in Arterial Hypertension

Goïta

Barca

Keïta

et al. 2020

Sci Rep

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Metabolomic studies have demonstrated the existence of biological signatures in blood of patients with arterial hypertension, but no study has hitherto reported the sexual dimorphism of these signatures. We compared the plasma metabolomic profiles of 28 individuals (13 women and 15 men) with essential arterial hypertension with those of a healthy control group (18 women and 18 men), using targeted metabolomics. Among the 188 metabolites explored, 152 were accurately measured. Supervised OPLS-DA (orthogonal partial least squares-discriminant analysis) showed good predictive performance for hypertension in both sexes (Q 2 cum = 0.59 in women and 0.60 in men) with low risk of overfitting (pvalue-CV ANOVA = 0.004 in women and men). Seventy-five and 65 discriminant metabolites with a VIP (variable importance for the projection) greater than 1 were evidenced in women and men, respectively. Both sexes showed a considerable increase in phosphatidylcholines, a decrease in C16:0 with an increase in C28:1 lysophosphatidylcholines, an increase in sphingomyelins, as well as an increase of symmetric dimethylarginine (SDMA), acetyl-ornithine and hydroxyproline. Twenty-nine metabolites, involved in phospholipidic and cardiac remodeling, arginine/nitric oxide pathway and antihypertensive and insulin resistance mechanisms, discriminated the metabolic sexual dimorphism of hypertension. Our results highlight the importance of sexual dimorphism in arterial hypertension.

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Identification of essential hypertension biomarkers in human urine by non-targeted metabolomics based on UPLC-Q-TOF/MS

Cited by 44 publications

References 37 publications

Urinary metabolic signatures reflect cardiovascular risk in the young, middle-aged, and elderly populations

Urinary metabolic signatures reflect cardiovascular risk in the young, middle-aged, and elderly populations

Establishment of the circadian metabolic phenotype strategy in spontaneously hypertensive rats: a dynamic metabolomics study

Sexual Dimorphism of Metabolomic Profile in Arterial Hypertension

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