Kynurenine Pathway Metabolites as Potential Clinical Biomarkers in Coronary Artery Disease

Abstract

Coronary artery disease (CAD) is one of the leading cause of mortality worldwide. Several risk factors including unhealthy lifestyle, genetic background, obesity, diabetes, hypercholesterolemia, hypertension, smoking, age, etc. contribute to the development of coronary atherosclerosis and subsequent coronary artery disease. Inflammation plays an important role in coronary artery disease development and progression. Pro-inflammatory signals promote the degradation of tryptophan via the kynurenine pathway resulting in the formation of several immunomodulatory metabolites. An unbalanced kynurenic pathway has been implicated in the pathomechanisms of various diseases including CAD. Significant improvements in detection methods in the last decades may allow simultaneous measurement of multiple metabolites of the kynurenine pathway and such a thorough analysis of the kynurenine pathway may be a valuable tool for risk stratification and determination of CAD prognosis. Nevertheless, imbalance in the activities of different branches of the kynurenine pathway may require careful interpretation. In this review, we aim to summarize clinical evidence supporting a possible use of kynurenine pathway metabolites as clinical biomarkers in various manifestations of CAD.

Keywords: IDO activity/detection; ischemic heart disease; kynurenic acid; liquid chromatography; mass spectrometry; personalized medicine; prediction; tryptophan.

Figure 1

Schematic overview of the kynurenine pathway. Enzymes are indicated in italics. AA, anthranilic acid; ACMSD, aminocarboxymuconate-semialdehyde-decarboxylase; AMO, anthranilate 3-monooxygenase; 3-HAA, 3-hydroxyanthranilic acid; 3-HAO, 3-hydroxyanthranilate 3,4-dioxygenase; 3-HK, 3-hydroxykynurenine; IDO1 and or, IDO2, indoleamine 2,3-dioxygenase-1 and -2; KATs, kynurenine aminotransferase enzymes; KMO, kynurenine monooxygenase; KYN, kynurenine; KYNA, kynurenic acid; NAM, nicotinamide adenine mononucleotide; PA, picolinic acid; QA, quinolinic acid; QPRT, quinolinate phosphoribosyltransferase; TDO, tryptophan-2,3-dioxygenase; Trp, Tryptophan; XA, xanthurenic acid.