Dysregulated tryptophan metabolism contributes to abdominal aortic aneurysm formation in mice. (2017) Digest
From the article:
“Our data found a previously undescribed causative role for 3-hydroxyanthranilic acid (3-HAA), a product of tryptophan metabolism, in abdominal aortic aneurysm formation,” said Dr. Ming-Hui Zou, director of the Center for Molecular and Translational Medicine at Georgia State and a Georgia Research Alliance Eminent Scholar in Molecular Medicine. “We believe agents that alter tryptophan metabolism may have therapeutic potential for preventing or treating abdominal aortic aneurysm. Our findings suggest that reducing 3-HAA may be a new target for treating cardiovascular diseases.”
The kynurenine pathway is the major route for the metabolism of tryptophan, and other studies have found this pathway plays a key role in the increased prevalence of cardiovascular disease. The researchers sought to identify the role of the kynurenine pathway and its products in angiotensin II (AngII)-induced abdominal aortic aneurysm. AngII is a hormone that increases blood pressure by constricting the blood vessels and is the principal mediator for the development and progression of abdominal aortic aneurysm.
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The researchers generated mice with genetic deficiencies by crossbreeding, and then infused the mice with AngII.
The study is the first to show that genetic deletion of indoleamine 2,3-dioxygenase (IDO) or the decrease in the gene expression of kynureninase (KNU) in the body restrained AngII-induced abdominal aortic aneurysm in mice deficient in apolipoprotein e.
In addition, the researchers made the discovery that 3-HAA was responsible for AngII-induced abdominal aortic aneurysm in the body.