Analysis of urinary exosomal metabolites identifies cardiovascular risk signatures with added value to urine analysis

Autor: Gloria Alvarez-Llamas, Paula J. Martinez, Aranzazu Santiago-Hernandez, Marta Martin-Lorenzo, Marta Agudiez, Juan M. García-Segura, Dolores Molero, Gonzalo Aldamiz-Echevarria, Angeles Heredero
Rok vydání: 2020
Předmět:
Bioquímica
Adult
Male
Nefrología y urología
Physiology
Metabolite
Urinary system
Plant Science
Urine
Cardiología
Urinalysis
030204 cardiovascular system & hematology
Biology
Exosomes
General Biochemistry
Genetics and Molecular Biology
03 medical and health sciences
chemistry.chemical_compound
0302 clinical medicine
Risk Factors
Structural Biology
Metabolites
Metabolome
Humans
Analytical strategy
lcsh:QH301-705.5
Ecology
Evolution
Behavior and Systematics
Aged
030304 developmental biology
0303 health sciences
Cell Biology
Metabolism
Middle Aged
Cardiovascular risk
NMR
Microvesicles
lcsh:Biology (General)
Biochemistry
chemistry
Cardiovascular Diseases
Subclinical atherosclerosis
Female
General Agricultural and Biological Sciences
Biomarkers
Research Article
Developmental Biology
Biotechnology
Zdroj: BMC Biology
E-Prints Complutense. Archivo Institucional de la UCM
instname
BMC Biology, Vol 18, Iss 1, Pp 1-9 (2020)
E-Prints Complutense: Archivo Institucional de la UCM
Universidad Complutense de Madrid
ISSN: 1741-7007
DOI: 10.1186/s12915-020-00924-y
Popis: Background Subclinical atherosclerosis may result in fatal cardiovascular (CV) events, but the underlying mechanisms and molecular players leading to disease are not entirely understood. Thus, novel approaches capable of identifying the factors involved in pathological progression and providing a better understanding of the subjacent mechanisms are needed. Extracellular vesicles (EVs) have been shown to have numerous biological functions, and their metabolome has recently generated interest as a source of novel biomarkers. The metabolic content of the exosomes has been so far unexplored in cardiovascular disease (CVD), and here, we developed an analytical strategy aimed at probing urinary exosomal metabolite content and its association to CV risk. Results Direct analysis of the exosomes without metabolite extraction was evaluated by high-resolution magic angle spinning (1H HR-MAS). Other two methodologies for the analysis of exosomal metabolites by 1H NMR were set up, based on methanol or organic solvents sequential extraction. The three methods were compared in terms of the number of detected signals and signal to noise ratio (S/N). The methanol method was applied to identify altered metabolites in the urinary exosomes of subjects with programmed coronary artery by-pass grafting (CABG) versus a control group. Target mass spectrometry (MS) was also performed for differential analysis. The clinical performance of exosomal metabolites of interest in CVD was investigated, and the added value of the exosomes compared to urine analysis was evaluated. Based on S/N ratio, simplicity, reproducibility, and quality of the spectrum, the methanol method was chosen for the study in CVD. A cardiometabolic signature composed by 4-aminohippuric acid, N-1-methylnicotinamide, and citric acid was identified in urinary exosomes. Directly in urine, 4-aminohippuric acid and citric acid do not show variation between groups and changes in N-1-methylnicotinamide are less pronounced, proving the added value of exosomes. Conclusions We set up a novel methodology to analyze metabolic alterations in urinary exosomes and identified a cardiometabolic signature in these microvesicles. This study constitutes the first evidence of a role for the exosomal metabolism in CVD and demonstrates the possibility to evaluate the urinary exosomal metabolic content by NMR and MS.
Databáze: OpenAIRE
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