Abstract
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.
Highlights
Cardiovascular disease continues being the leading cause of premature death worldwide despite continuing efforts in primary prevention
A cohort of subjects with programmed coronary artery bypass grafting (CABG) was recruited as a representative pop3
[10], and in urinein from subjects aorta from atherosclerotic rabbits [12,13], in urine from hypertensive subjects with higher at the onset of an acute coronary syndrome [12] were here analyzed by targeted mass cardiovascular risk in terms of albuminuria development [10], and in urine from subjects spectrometry to investigate their alteration during human atherosclerosis development
Summary
Cardiovascular disease continues being the leading cause of premature death worldwide despite continuing efforts in primary prevention. Antioxidants 2021, 10, 1369 silently and asymptomatically, making it extremely challenging to promptly identify those individuals at high cardiovascular risk to prevent a fatal event. Despite that over 50% of the observed decrease in mortality caused by coronary heart disease can be attributed to changes in those risk factors, further knowledge is needed to better stratify individual risk and improve prevention [1,2]. No early diagnostic markers are available to date that may undoubtedly predict future events on healthy subjects or stratify individual risk. In this clinical scenario, there is an urgent need to find out novel molecular indicators, alone or combined with existing ones, together with a better knowledge of the operating mechanisms in atherosclerosis development
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