Deregulated tryptophan-kynurenine pathway is linked to inflammation oxidative stress and immune activation pathway in cardiovascular diseases

摘要

The kynurenine (Kyn) pathway is the major route for tryptophan (Trp) metabolism, and it contributes to several fundamental biological processes. Trp is constitutively oxidized by tryptophan 2, 3-dioxygenase in liver cells. In other cell types, it is catalyzed by an alternative inducible indoleamine-pyrrole 2, 3-dioxygenase (IDO) under certain pathophysiological conditions, which consequently increases the formation of Kyn metabolites. IDO is up-regulated in response to inflammatory conditions as a novel marker of immune activation in early atherosclerosis. Besides, IDO and the IDO-related pathway are important mediators of the immunoinflammatory responses in advanced atherosclerosis. In particular, Kyn, 3-hydroxykynurenine, and quinolinic acid are positively associated with inflammation, oxidative stress (SOX), endothelial dysfunction, and carotid artery intima-media thickness values in end-stage renal disease patients. Moreover, IDO is a potential novel contributor to vessel relaxation and metabolism in systemic infections, which is also activated in acute severe heart attacks. The Kyn pathway plays a key role in the increased prevalence of cardiovascular disease by regulating inflammation, SOX, and immune activation.