The role of the kynurenine pathway of tryptophan metabolism in cardiovascular disease

Summary

Coronary heart disease and stroke, the deadliest forms of cardiovascular disease (CVD), are mainly caused by atherosclerosis, a chronic inflammatory disease of the artery wall driven by maladaptive immune responses in the vessel wall. Various risk factors for CVD influence this pathogenic process, including diabetes mellitus, hypertension, dyslipidaemia, and obesity. Indoleamine 2,3-dioxygenase (IDO), an enzyme catalyzing the rate-limiting step in the kynurenine pathway of tryptophan degradation, is strongly induced by inflammation in several tissues, including the artery wall. An increasing body of evidence indicates that IDO promotes immune tolerance, decreases inflammation, and functions as a homeostatic mechanism against excessive immune reactions.

This review provides an overview of the emerging field of the kynurenine pathway of tryptophan degradation in CVD, emphasizing the role of IDO-mediated tryptophan metabolism and its metabolites in the modulation of ‘classical’ cardiovascular risk factors, such as hypertension, obesity, lipid metabolism, diabetes mellitus, and in the development of atherosclerotic CVD.

Zusammenfassung

Ursache der koronaren Herzkrankheit und des Schlaganfalls, den tödlichsten Formen der Herz-Kreislauf-Krankheit (CVD), ist vor allem die Atherosklerose, eine chronisch-entzündliche Erkrankung der Arterienwand, die durch eine maladaptive Immunantwort in der Gefäßwand in Gang gehalten wird. Verschiedene Risikofaktoren für CVD beeinflussen diesen Krankheitsprozess, darunter Diabetes mellitus, Hypertonie, Dyslipidämie und Adipositas. Die Indolamin-2,3-Dioxygenase (IDO) ist ein Enzym, das als Katalysator für den umsatzlimitierenden Schritt im Kynurenin-Stoffwechselweg beim Abbau von Tryptophan dient und in verschiedenen Geweben, u. a. der Gefäßwand, infolge entzündlicher Vorgänge stark aktiviert wird. Es mehren sich die Belege dafür, dass IDO die Immuntoleranz fördert, Entzündungen reduziert und eine ausgleichende Funktion gegen überschießende Immunreaktionen hat.

In diesem Review geben wir einen Überblick über das neue Forschungsgebiet zum Kynurenin-Stoffwechselweg des Tryptophanabbaus bei CVD, mit Schwerpunkt auf der Rolle des IDO-vermittelten Stoffwechsels von Tryptophan und seiner Abbauprodukte bei der Modulation “klassischer” kardiovaskulärer Risikofaktoren wie Hypertonie, Adipositas, Lipidstoffwechsel oder Diabetes mellitus, und bei der Entwicklung einer atherosklerotischen CVD.

Keywords

Tryptophan - kynurenine - indoleamine - inflammation - cardiovascular - atherosclerosis - obesity - diabetes - lipids - cholesterol - hypertension - stroke

Schlüsselwörter

Tryptophan - Kynurenin - Indolamin - Entzündung - kardiovaskulär - Atherosklerose - Adipositas - Diabetes - Lipide - Cholesterin - Hyper tonie - Schlaganfall

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