Association between altered tryptophan metabolism, plasma aryl hydrocarbon receptor agonists, and inflammatory Chagas disease.

Introduction: Chagas disease causes a cardiac illness characterized by immunoinflammatory reactions leading to myocardial fibrosis and remodeling. The development of Chronic Chagas Cardiomyopathy (CCC) in some patients while others remain asymptomatic is not fully understood, but dysregulated inflammatory responses are implicated. The Aryl hydrocarbon receptor (AhR) plays a crucial role in regulating inflammation.

Infection Promotes Vascular Remodeling and Coexpression of α-Smooth Muscle Actin and Macrophage Markers in Cells of the Aorta.

Chagas disease is an emerging global health problem; however, it remains neglected. Increased aortic stiffness (IAS), a predictor of cardiovascular events, has recently been reported in asymptomatic chronic Chagas patients. After vascular injury, smooth muscle cells (SMCs) can undergo alterations associated with phenotypic switch and transdifferentiation, promoting vascular remodeling and IAS.

Wnt Signaling Plays a Key Role in the Regulation of the Immune Response and Cardiac Damage during Infection.

Chagas cardiomyopathy is the consequence of a compromised electrical and mechanical cardiac function, with parasite persistence, unbalanced inflammation, and pathological tissue remodelling, being intricately related to myocardial aggression and impaired function. Recent studies have shown that Wnt signaling pathways play a critical role in the pathogenesis of cardiac and vascular diseases. In addition, we have reported that infection activates Wnt signaling to promote intracellular replication of the parasites in macrophages, with the treatment of mice with IWP-L6 (an inhibitor of the -acyl-transferase, PORCN, responsible for the post-translational modifications necessary for Wnt protein secretion) being able to diminish parasitemia and tissue parasitism.