Indoleamine 2 3-dioxygenase knockout limits angiotensin II-induced aneurysm in low density lipoprotein receptor-deficient mice fed with high fat diet

PloS One
Sarvenaz MetghalchiSoraya Taleb

Abstract

Abdominal aortic aneurysm (AAA) is an age-associated disease characterized by chronic inflammation, vascular cell apoptosis and metalloproteinase-mediated extracellular matrix degradation. Despite considerable progress in identifying targets involved in these processes, therapeutic approaches aiming to reduce aneurysm growth and rupture are still scarce. Indoleamine 2-3 dioxygenase 1 (IDO) is the first and rate-limiting enzyme involved in the conversion of tryptophan (Trp) into kynurenine (Kyn) pathway. In this study, we investigated the role of IDO in two different models of AAA in mice. Mice with deficiencies in both low density receptor-deficient (Ldlr-/-) and IDO (Ldlr-/-Ido1-/-) were generated by cross-breeding Ido1-/- mice with Ldlr-/-mice. To induce aneurysm, these mice were infused with angiotensin II (Ang II) (1000 ng/min/kg) and fed with high fat diet (HFD) during 28 days. AAAs were present in almost all Ldlr-/- infused with AngII, but only in 50% of Ldlr-/-Ido1-/- mice. Immunohistochemistry at an early time point (day 7) revealed no changes in macrophage and T lymphocyte infiltration within the vessel wall, but showed reduced apoptosis, as assessed by TUNEL assay, and increased α-actin staining within the media of Ld...Continue Reading

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Citations

Sep 26, 2019·Frontiers in Immunology·Soraya Taleb
Nov 30, 2019·Frontiers in Immunology·Fanni A Boros, László Vécsei
Dec 11, 2020·Journal of Atherosclerosis and Thrombosis·Masanori NishimuraYujiro Asada
Feb 19, 2021·Journal of Vascular Surgery·Baohui XuRonald L Dalman
Feb 23, 2021·Frontiers in Cardiovascular Medicine·Yangfeng HouJing Wang

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Methods Mentioned

BETA
PCR
flow cytometry

Software Mentioned

Microvisions
Histolab

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