Tryptophan Metabolism, Inflammation, and Oxidative Stress in Patients with Neurovascular Disease.

Martin Hajsl,Karolina Broulikova,Jiri Suttnar,Martin Sramek,Alzbeta Hlavackova,Jan E Dyr,Martin Maly,Martin Maly

doi:10.3390/metabo10050208

Abstract

Atherosclerosis is a leading cause of major vascular events, myocardial infarction, and ischemic stroke. Tryptophan (TRP) catabolism was recognized as an important player in inflammation and immune response having together with oxidative stress (OS) significant effects on each phase of atherosclerosis. The aim of the study is to analyze the relationship of plasma levels of TRP metabolites, inflammation, and OS in patients with neurovascular diseases (acute ischemic stroke (AIS), significant carotid artery stenosis (SCAS)) and in healthy controls. Blood samples were collected from 43 patients (25 with SCAS, 18 with AIS) and from 25 healthy controls. The concentrations of twelve TRP metabolites, riboflavin, neopterin (NEO, marker of inflammation), and malondialdehyde (MDA, marker of OS) were measured by liquid chromatography–tandem mass spectrometry (LC-MS/MS). Concentrations of seven TRP metabolites (TRP, kynurenine (KYN), 3-hydroxykynurenine (3-HK), 3-hydroxyanthranilic acid (3-HAA), anthranilic acid (AA), melatonin (MEL), tryptamine (TA)), NEO, and MDA were significantly different in the studied groups. Significantly lower concentrations of TRP, KYN, 3-HAA, MEL, TA, and higher MDA concentrations were found in AIS compared to SCAS patients. MDA concentration was higher in both AIS and SCAS group (p < 0.001, p = 0.004, respectively) compared to controls, NEO concentration was enhanced (p < 0.003) in AIS. MDA did not directly correlate with TRP metabolites in the study groups, except for 1) a negative correlation with kynurenine acid and 2) the activity of kynurenine aminotransferase in AIS patients (r = −0.552, p = 0.018; r = −0.504, p = 0.033, respectively). In summary, TRP metabolism is clearly more deregulated in AIS compared to SCAS patients; the effect of TRP metabolites on OS should be further elucidated.

Highlights

Atherosclerotic vascular diseases (ASVD) are the leading cause of death worldwide
Since TRP catabolism was recognized as an important player in inflammation and its metabolites with either prooxidant and antioxidant properties should have relationship with oxidative stress (OS), in this study we aim to compare the similarities and differences in TRP metabolism, inflammation, and OS in patients with acute ischemic stroke (AIS), more rarely studied significant carotid artery stenosis (SCAS) and in healthy controls
In this work patients with SCAS, AIS, and controls were compared with respect to TRP metabolism, inflammation, OS, and RBF

Summary

Introduction

Atherosclerotic vascular diseases (ASVD) are the leading cause of death worldwide. The most severe forms of ASVD are acute coronary syndrome and acute ischemic stroke, which are caused by superimposed thrombosis on underlying atherosclerotic plaque. Metabolites 2020, 10, 208 and production of reactive oxygen species (ROS) [1,2,3]. Both immune and inflammatory responses together with oxidative stress (OS) have significant effects on every phase of atherosclerosis [4,5]. Tryptophan (TRP) catabolism via the kynurenine (KYN) pathway (KP) was recognized as an important player in inflammation and immune response [6,7,8,9,10]. TDO was found to catalyze TRP breakdown under basal conditions, while IDO-1, with key role in immune regulation, is induced and regulated by several stimuli, such as inflammatory signals [13]

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