Cargando…
Metabolic Alterations Identified in Urine, Plasma and Aortic Smooth Muscle Cells Reflect Cardiovascular Risk in Patients with Programmed Coronary Artery Bypass Grafting
Atherosclerosis is the predominant pathology associated to premature deaths due to cardiovascular disease. However, early intervention based on a personalized diagnosis of cardiovascular risk is very limited. We have previously identified metabolic alterations during atherosclerosis development in a...
Autores principales: | , , , , , , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2021
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8466954/ https://www.ncbi.nlm.nih.gov/pubmed/34573001 http://dx.doi.org/10.3390/antiox10091369 |
_version_ | 1784573272871927808 |
---|---|
author | Santiago-Hernandez, Aranzazu Martinez, Paula J. Agudiez, Marta Heredero, Angeles Gonzalez-Calero, Laura Yuste-Montalvo, Alma Esteban, Vanesa Aldamiz-Echevarria, Gonzalo Martin-Lorenzo, Marta Alvarez-Llamas, Gloria |
author_facet | Santiago-Hernandez, Aranzazu Martinez, Paula J. Agudiez, Marta Heredero, Angeles Gonzalez-Calero, Laura Yuste-Montalvo, Alma Esteban, Vanesa Aldamiz-Echevarria, Gonzalo Martin-Lorenzo, Marta Alvarez-Llamas, Gloria |
author_sort | Santiago-Hernandez, Aranzazu |
collection | PubMed |
description | Atherosclerosis is the predominant pathology associated to premature deaths due to cardiovascular disease. However, early intervention based on a personalized diagnosis of cardiovascular risk is very limited. We have previously identified metabolic alterations during atherosclerosis development in a rabbit model and in subjects suffering from an acute coronary syndrome. Here we aim to identify specific metabolic signatures which may set the basis for novel tools aiding cardiovascular risk diagnosis in clinical practice. In a cohort of subjects with programmed coronary artery bypass grafting (CABG), we have performed liquid chromatography and targeted mass spectrometry analysis in urine and plasma. The role of vascular smooth muscle cells from human aorta (HA-VSMCs) was also investigated by analyzing the intra and extracellular metabolites in response to a pro-atherosclerotic stimulus. Statistically significant variation was considered if p value < 0.05 (Mann-Whitney test). Urinary trimethylamine N-oxide (TMAO), arabitol and spermidine showed higher levels in the CVrisk group compared with a control group; while glutamine and pantothenate showed lower levels. The same trend was found for plasma TMAO and glutamine. Plasma choline, acetylcholine and valine were also decreased in CVrisk group, while pyruvate was found increased. In the secretome of HA-VSMCs, TMAO, pantothenate, glycerophosphocholine, glutathion, spermidine and acetylcholine increased after pro-atherosclerotic stimulus, while secreted glutamine decreased. At intracellular level, TMAO, pantothenate and glycerophosphocholine increased with stimulation. Observed metabolic deregulations pointed to an inflammatory response together with a deregulation of oxidative stress counteraction. |
format | Online Article Text |
id | pubmed-8466954 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-84669542021-09-27 Metabolic Alterations Identified in Urine, Plasma and Aortic Smooth Muscle Cells Reflect Cardiovascular Risk in Patients with Programmed Coronary Artery Bypass Grafting Santiago-Hernandez, Aranzazu Martinez, Paula J. Agudiez, Marta Heredero, Angeles Gonzalez-Calero, Laura Yuste-Montalvo, Alma Esteban, Vanesa Aldamiz-Echevarria, Gonzalo Martin-Lorenzo, Marta Alvarez-Llamas, Gloria Antioxidants (Basel) Article Atherosclerosis is the predominant pathology associated to premature deaths due to cardiovascular disease. However, early intervention based on a personalized diagnosis of cardiovascular risk is very limited. We have previously identified metabolic alterations during atherosclerosis development in a rabbit model and in subjects suffering from an acute coronary syndrome. Here we aim to identify specific metabolic signatures which may set the basis for novel tools aiding cardiovascular risk diagnosis in clinical practice. In a cohort of subjects with programmed coronary artery bypass grafting (CABG), we have performed liquid chromatography and targeted mass spectrometry analysis in urine and plasma. The role of vascular smooth muscle cells from human aorta (HA-VSMCs) was also investigated by analyzing the intra and extracellular metabolites in response to a pro-atherosclerotic stimulus. Statistically significant variation was considered if p value < 0.05 (Mann-Whitney test). Urinary trimethylamine N-oxide (TMAO), arabitol and spermidine showed higher levels in the CVrisk group compared with a control group; while glutamine and pantothenate showed lower levels. The same trend was found for plasma TMAO and glutamine. Plasma choline, acetylcholine and valine were also decreased in CVrisk group, while pyruvate was found increased. In the secretome of HA-VSMCs, TMAO, pantothenate, glycerophosphocholine, glutathion, spermidine and acetylcholine increased after pro-atherosclerotic stimulus, while secreted glutamine decreased. At intracellular level, TMAO, pantothenate and glycerophosphocholine increased with stimulation. Observed metabolic deregulations pointed to an inflammatory response together with a deregulation of oxidative stress counteraction. MDPI 2021-08-27 /pmc/articles/PMC8466954/ /pubmed/34573001 http://dx.doi.org/10.3390/antiox10091369 Text en © 2021 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Santiago-Hernandez, Aranzazu Martinez, Paula J. Agudiez, Marta Heredero, Angeles Gonzalez-Calero, Laura Yuste-Montalvo, Alma Esteban, Vanesa Aldamiz-Echevarria, Gonzalo Martin-Lorenzo, Marta Alvarez-Llamas, Gloria Metabolic Alterations Identified in Urine, Plasma and Aortic Smooth Muscle Cells Reflect Cardiovascular Risk in Patients with Programmed Coronary Artery Bypass Grafting |
title | Metabolic Alterations Identified in Urine, Plasma and Aortic Smooth Muscle Cells Reflect Cardiovascular Risk in Patients with Programmed Coronary Artery Bypass Grafting |
title_full | Metabolic Alterations Identified in Urine, Plasma and Aortic Smooth Muscle Cells Reflect Cardiovascular Risk in Patients with Programmed Coronary Artery Bypass Grafting |
title_fullStr | Metabolic Alterations Identified in Urine, Plasma and Aortic Smooth Muscle Cells Reflect Cardiovascular Risk in Patients with Programmed Coronary Artery Bypass Grafting |
title_full_unstemmed | Metabolic Alterations Identified in Urine, Plasma and Aortic Smooth Muscle Cells Reflect Cardiovascular Risk in Patients with Programmed Coronary Artery Bypass Grafting |
title_short | Metabolic Alterations Identified in Urine, Plasma and Aortic Smooth Muscle Cells Reflect Cardiovascular Risk in Patients with Programmed Coronary Artery Bypass Grafting |
title_sort | metabolic alterations identified in urine, plasma and aortic smooth muscle cells reflect cardiovascular risk in patients with programmed coronary artery bypass grafting |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8466954/ https://www.ncbi.nlm.nih.gov/pubmed/34573001 http://dx.doi.org/10.3390/antiox10091369 |
work_keys_str_mv | AT santiagohernandezaranzazu metabolicalterationsidentifiedinurineplasmaandaorticsmoothmusclecellsreflectcardiovascularriskinpatientswithprogrammedcoronaryarterybypassgrafting AT martinezpaulaj metabolicalterationsidentifiedinurineplasmaandaorticsmoothmusclecellsreflectcardiovascularriskinpatientswithprogrammedcoronaryarterybypassgrafting AT agudiezmarta metabolicalterationsidentifiedinurineplasmaandaorticsmoothmusclecellsreflectcardiovascularriskinpatientswithprogrammedcoronaryarterybypassgrafting AT herederoangeles metabolicalterationsidentifiedinurineplasmaandaorticsmoothmusclecellsreflectcardiovascularriskinpatientswithprogrammedcoronaryarterybypassgrafting AT gonzalezcalerolaura metabolicalterationsidentifiedinurineplasmaandaorticsmoothmusclecellsreflectcardiovascularriskinpatientswithprogrammedcoronaryarterybypassgrafting AT yustemontalvoalma metabolicalterationsidentifiedinurineplasmaandaorticsmoothmusclecellsreflectcardiovascularriskinpatientswithprogrammedcoronaryarterybypassgrafting AT estebanvanesa metabolicalterationsidentifiedinurineplasmaandaorticsmoothmusclecellsreflectcardiovascularriskinpatientswithprogrammedcoronaryarterybypassgrafting AT aldamizechevarriagonzalo metabolicalterationsidentifiedinurineplasmaandaorticsmoothmusclecellsreflectcardiovascularriskinpatientswithprogrammedcoronaryarterybypassgrafting AT martinlorenzomarta metabolicalterationsidentifiedinurineplasmaandaorticsmoothmusclecellsreflectcardiovascularriskinpatientswithprogrammedcoronaryarterybypassgrafting AT alvarezllamasgloria metabolicalterationsidentifiedinurineplasmaandaorticsmoothmusclecellsreflectcardiovascularriskinpatientswithprogrammedcoronaryarterybypassgrafting |