Role of intestinal indoleamine 2, 3-dioxygenase 1 in atherosclerosis - 18/05/21
Résumé |
Introduction |
The prevalence of high fat diet (HFD)-induced metabolic syndrome is booming contributing to persist increase of cardiovascular diseases, including atherosclerosis. Indoleamine 2, 3-dioxygenase 1 (IDO) is the main enzyme responsible for tryptophan (Trp) degradation in the extrahepatic organs, including intestine. Our team has recently shown that the total invalidation of IDO under HFD reduced metabolic complications through shaping gut microbiota. However the specific role of IDO expressed in the gut on the development of cardiometabolic disease is unknown.
Objective |
Study the impact of intestinal IDO on atherosclerosis development under different atherogenic diets either high cholesterol (HC) or a combination of HC and HFD (HFD+HC).
Methods |
We have created a mouse model susceptible to develop atherosclerosis bearing the specific deletion of IDO in intestinal epithelial cells (IEC), known to be the major cells expressing IDO in the gut. The KO mice (Ldlr−/− (low density lipoprotein receptor KO) Ido-1flox/floxvillin cre+) and the controls (Ldlr−/−Ido-1flox/flox villin cre-) were fed either with HFD+HC or HC diet during short time or long time. The feces were collected to characterize microbiota as well as its derived metabolites. The heart and aorta were retrieved to analyze plaque size and composition.
Results |
Unexpectedly, IDO invalidation in IEC leads to a significant increase in plaque size in aortic sinus at 8 weeks, in the condition of HFD+HC and not HC diet, without significant changes of plasma cholesterol levels. This was associated with a higher infiltration of inflammatory cells as well as a significant decrease in the expression of main actors involved in intestinal homeostasis such as the antimicrobial peptides (Reg3b, Reg3g) and tight junction protein such as occludin in the intestines of KO mice.
Conclusion |
The expression of IDO in IEC has a protective effects locally in intestine and also prevents the development of atherosclerosis.
Le texte complet de cet article est disponible en PDF.Plan
Vol 13 - N° 2
P. 175 - mai 2021 Retour au numéroBienvenue sur EM-consulte, la référence des professionnels de santé.