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

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.