Indoleamine 2,3-dioxygenase-1, a Novel Therapeutic Target for Post-Vascular Injury Thrombosis in CKD.

ABSTRACT:

Background

CKD, characterized by retained uremic solutes, is a strong and independent risk factor for thrombosis after vascular procedures . Urem ic solutes such as indoxyl sulfate (IS) and kynurenine (Kyn) mediate prothrombotic effect through tissue factor (TF). IS and Kyn biogenesis depends on multiple enzymes, with therapeutic implications unexplored. We examined the role of indoleamine 2,3-dioxygenase-1 (IDO-1), a rate-limiting enzyme of kynurenine biogenesis, in CKD-associated thrombosis after vascular injury.

Methods

IDO-1 expression in mice and human vessels was examined. IDO-1^-/- mice, IDO-1 inhibitors, an adenine-induced CKD, and carotid artery injury models were used.

Results

Both global IDO-1^-/- CKD mice and IDO-1 inhibitor in wild-typ

SUBMITTER: Walker JA 

PROVIDER: S-EPMC8806102 | biostudies-literature | 2021 Nov

REPOSITORIES: biostudies-literature