A Pilot Study on the 1H-NMR Serum Metabolic Profile of Takotsubo Patients Reveals Systemic Response to Oxidative Stress

Abstract

Takotsubo syndrome (TTS) presents as an acute coronary syndrome characterized by severe left ventricular (LV) dysfunction and non-obstructive coronary artery disease that typically shows spontaneous recovery within days or weeks. The mechanisms behind TTS are mainly related to beta-adrenergic overstimulation and acute endogenous catecholamine surge, both of which could increase oxidative status that may induce further deterioration of cardiac function. Although several studies reported evidence of inflammation and oxidative stress overload in myocardial tissue of TTS models, systemic biochemical evidence of augmented oxidant activity in patients with TTS is lacking. In this study, serum samples of ten TTS patients and ten controls have been analyzed using 1H-NMR spectroscopy. The results of this pilot study show a marked alteration in the systemic metabolic profile of TTS patients, mainly characterized by significant elevation of ketone bodies, 2-hydroxybutyrate, acetyl-L-carnitine, and glutamate levels, in contrast with a decrease of several amino acid levels. The overall metabolic fingerprint reflects a systemic response to oxidative stress caused by the stressor that triggered the syndrome’s onset.

Takotsubo Syndrome and Coronary Artery Disease: Which Came First—The Chicken or the Egg?

“…Reduced synthesis of Kreb's cycle intermediates and adenosine triphosphate results from an increase in myocardial glucose intake combined with a decrease in the available glycolysis metabolites, giving rise to a different metabolic profile in TTS than patients with AMI [28]. In a recent study, serum metabolic profile analysis showed that TTS is associated with a substantial rise in the plasmatic concentrations of ketone bodies, 2-hydroxybutyrate, and markers associated with fatty acid metabolism, which leads to endothelial dysfunction through the production of oxygen radicals and vascular inflammation [29][30][31]. Additionally, TTS patients have decreased concentrations of several amino acids, which are correlated in a proportionate way with LV systolic function [29,32].…”

“…In a recent study, serum metabolic profile analysis showed that TTS is associated with a substantial rise in the plasmatic concentrations of ketone bodies, 2-hydroxybutyrate, and markers associated with fatty acid metabolism, which leads to endothelial dysfunction through the production of oxygen radicals and vascular inflammation [29][30][31]. Additionally, TTS patients have decreased concentrations of several amino acids, which are correlated in a proportionate way with LV systolic function [29,32].…”

Biomarkers of Oxidative Stress in Acute and Chronic Diseases

“…Our Special Issue presents innovative research [ 1 , 2 , 3 , 4 , 5 , 6 , 7 , 8 , 9 , 10 , 11 , 12 ] and review [ 13 , 14 , 15 ] papers addressing many of these questions related to the fundamental OS involvement in the onset and progression of several acute and chronic diseases, and about the correlated biomarkers and potential therapies. Precisely, the 12 research articles [ 1 , 2 , 3 , 4 , 5 , 6 , 7 , 8 , 9 , 10 , 11 , 12 ] included in this Special Issue are focused on evidencing the OS role in diagnostics, signatures of the disease course, molecules involved, OS potential treatments and effects, and short- and long-term consequences.…”

“…Our Special Issue presents innovative research [ 1 , 2 , 3 , 4 , 5 , 6 , 7 , 8 , 9 , 10 , 11 , 12 ] and review [ 13 , 14 , 15 ] papers addressing many of these questions related to the fundamental OS involvement in the onset and progression of several acute and chronic diseases, and about the correlated biomarkers and potential therapies. Precisely, the 12 research articles [ 1 , 2 , 3 , 4 , 5 , 6 , 7 , 8 , 9 , 10 , 11 , 12 ] included in this Special Issue are focused on evidencing the OS role in diagnostics, signatures of the disease course, molecules involved, OS potential treatments and effects, and short- and long-term consequences. Precisely, Chen et al [ 1 ], by performing a nano-electrospray ionization–mass spectrometry (nanoESI-MS)-based lipidomic profiling study on lipid accumulation and oxidation in kidney cells in the chronic kidney disease (CKD) model, confirmed the key role of OS and lipid dysregulation in renal lipid droplet (LD) alteration at the molecular level.…”

“…Interestingly, Cicero et al [ 8 ] performing a pilot study, and using 1 H-NMR spectroscopy, evidenced a typical metabolic profile characterized by a significant increment in circulating KB, ALCAR, glutamate, and Phe/Tyr ratio, and a decrease in total amino acids, histidine, arginine, alanine, and methionine, in patients affected by Takotsubo syndrome. Based on this result, they can envisage that the future inclusion of metabolic markers in clinical practice might improve risk stratification in TTS.…”