Cytoskeleton deregulation and impairment in amino acids and energy metabolism in early atherosclerosis at aortic tissue with reflection in plasma

Martin‐Lorenzo, Marta; González-Calero, Laura; Maroto, Aroa S.; Martínez, Pedro Luis Moreno; Zubiri, Irene; Cuesta, Fernando de la; Mouriño-Álvarez, Laura; Barderas, María G.; Heredero, Angeles; Aldamiz-Echevarría, Gonzalo; Vivanco, Fernando; Alvarez-Llamas, Gloria

doi:10.1016/j.bbadis.2015.12.006

Cited by 34 publications

(37 citation statements)

References 51 publications

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“…Urine samples from 63 hypertensive patients under chronic RAS suppression were analyzed, individually (not pools), by label-free SRM-LC-MS/MS (selected reaction monitoring) as previously published (see Supplementary Table 8 for details) 17 , 18 , 54 , 55 . Briefly, in-silico digestion of the protein of interest was done with Skyline software.…”

Section: Methodsmentioning

confidence: 99%

Immune system deregulation in hypertensive patients chronically RAS suppressed developing albuminuria

Martin‐Lorenzo

González-Calero

Martínez

et al. 2017

Sci Rep

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Albuminuria development in hypertensive patients is an indicator of higher cardiovascular (CV) risk and renal damage. Chronic renin-angiotensin system (RAS) suppression facilitates blood pressure control but it does not prevent from albuminuria development. We pursued the identification of protein indicators in urine behind albuminuria development in hypertensive patients under RAS suppression. Urine was collected from 100 patients classified in three groups according to albuminuria development: (a) patients with persistent normoalbuminuria; (b) patients developing de novo albuminuria; (c) patients with maintained albuminuria. Quantitative analysis was performed in a first discovery cohort by isobaric labeling methodology. Alterations of proteins of interest were confirmed by target mass spectrometry analysis in an independent cohort. A total of 2416 proteins and 1223 functional categories (coordinated protein responses) were identified. Immune response, adhesion of immune and blood cells, and phagocytosis were found significantly altered in patients with albuminuria compared to normoalbuminuric individuals. The complement system C3 increases, while Annexin A1, CD44, S100A8 and S100A9 proteins showed significant diminishment in their urinary levels when albuminuria is present. This study reveals specific links between immune response and controlled hypertension in patients who develop albuminuria, pointing to potential protein targets for novel and future therapeutic interventions.

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Section: Methodsmentioning

confidence: 99%

Immune system deregulation in hypertensive patients chronically RAS suppressed developing albuminuria

Martin‐Lorenzo

González-Calero

Martínez

et al. 2017

Sci Rep

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“…Similarly, it was recently shown that a metabolomic signature characterized largely by intermediates of fatty acid oxidation improved the prediction of cardiovascular events in the elderly [ 17 ]. Using metabolomics approaches, we previously identified specific metabolic fingerprints in urine reflecting the development of atherosclerosis and acute coronary syndrome/patient recovery [ 18 ] and the cardiovascular risk of subjects undergoing coronary artery bypass surgery [ 19 ]. By proteomics, we recently identified a urinary cardiovascular risk signature in young adults based on six proteins [ 20 ].…”

Section: Introductionmentioning

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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“…Amino acids play an important role in the process of human metabolism, so they are important substances which are related to human health [1][2][3][4]. Studies have shown that amino acid metabolism diseases and malignant tumors had certain relevance to some tyrosine metabolite [5][6][7][8][9].…”

Section: Introductionmentioning

confidence: 99%

“…The results showed that some impurities could interfere with the analysis of the three target compounds when the samples were cleaned by method (1) or (2). Because in method (1), the membrane filter can only remove the insoluble impurities in the urine.…”

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Simultaneous determination of 4-hydroxyphenyl lactic acid, 4-hydroxyphenyl acetic acid, and 3,4-hydroxyphenyl propionic acid in human urine by ultra-high performance liquid chromatography with fluorescence detection

2017

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A simple and reliable method was established for simultaneous determination of 4-hydroxyphenyl acetic acid, 4-hydroxyphenyl lactic acid, and 3,4-hydroxyphenyl propionic acid in human urine by high-performance liquid chromatography with fluorescence detection. Solid-phase extraction was used to eliminate the interferences in urine. The separation of three analytes was achieved using a C column and a mobile phase formed by a 95:5 v/v mixture of 50 mmol/L ammonium acetate buffer at pH 6.8 that contained 5 mmol/L tetrabutyl ammonium bromide and acetonitrile. Under the optimized conditions, the detection limits of 4-hydroxyphenyl acetic acid, 4-hydroxyphenyl lactic acid, and 3,4-hydroxyphenyl propionic acid were 4.8 × 10 , 8.80 × 10 , and 9.00 × 10 mg/L, respectively, and the recoveries were in the range of 85.0-120.0% with relative standard deviations of 1.5-3.1%. This method was used to analyze urine samples from breast cancer patients, healthy people and post-surgery breast cancer patients. Significant differences in urinary levels of 4-hydroxyphenyl acetic acid and 4-hydroxyphenyl lactic acid could be found between the breast cancer patients group and other two groups. No effect of age and sex was observed on the urinary levels of 4-hydroxyphenyl acetic acid and 4-hydroxyphenyl lactic acid. This method might be helpful for cancer biomarkers discovery in urine.

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Cytoskeleton deregulation and impairment in amino acids and energy metabolism in early atherosclerosis at aortic tissue with reflection in plasma

Abstract: A specific molecular marker panel composed by PKM, valine and pyruvate is shown here linked to cardiovascular risk.

Cited by 34 publications

References 51 publications

Immune system deregulation in hypertensive patients chronically RAS suppressed developing albuminuria

Immune system deregulation in hypertensive patients chronically RAS suppressed developing albuminuria

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

Simultaneous determination of 4-hydroxyphenyl lactic acid, 4-hydroxyphenyl acetic acid, and 3,4-hydroxyphenyl propionic acid in human urine by ultra-high performance liquid chromatography with fluorescence detection

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