期刊
ANTIOXIDANTS
卷 10, 期 9, 页码 -出版社
MDPI
DOI: 10.3390/antiox10091369
关键词
cardiovascular risk; atherosclerosis; chronic kidney disease; vascular smooth muscle cells; oxidative stress; metabolites; metabolomics; biomarkers
资金
- FEDER [PI16/01334, PI18/00348, PI20/01103, IF08/3667-1, CPII15/00027, PT13/0001/0013]
- PRB3 [IPT17/0019-ISCIII-SGEFI/ERDF]
- REDinREN [RD16/0009]
- ARADyAL [RD/0006/0013]
- Fundacion SENEFRO/SEN
- CAM [PEJD-2019-PRE/BMD-16992, 2018-T2/BMD-11561, CM_P2018/BAAA4574]
- Fundacion Conchita Rabago de Jimenez Diaz
- Getinge Group Spain SL
- SEAIC [19_A08]
- Alfonso X el Sabio University Foundations
- Instituto de Salud Carlos III
Atherosclerosis is a major cause of premature deaths due to cardiovascular disease, with limited early intervention based on personalized diagnosis of cardiovascular risk. Metabolic alterations identified in subjects with cardiovascular risk may lead to novel tools aiding cardiovascular risk diagnosis in clinical practice, showing potential for inflammatory response and oxidative stress deregulation.
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.
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