期刊
FRONTIERS IN BIOSCIENCE-LANDMARK
卷 20, 期 -, 页码 1116-1143出版社
FRONTIERS IN BIOSCIENCE INC
DOI: 10.2741/4363
关键词
Kynurenines; Cardiovascular Diseases; Inflammation; Oxidative Stress; Immune Activation; Review
资金
- National Institutes of Health [RO1 HL110488, RO1 HL105157, RO1 HL096032, RO1 HL089920, RO1 HL080499, RO1 HL079584, RO1 HL074399]
- Warren Chair in Diabetes Research of the University of Oklahoma Health Sciences Center
- National Center of American Heart Association [11SDG5560036]
- Oklahoma Center for the Advancement of Science and Technology [HR12-061]
- National Established Investigator Award of the American Heart Association
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.
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