Alterations to the Cardiac Metabolome Induced by Chronic T. cruzi Infection Relate to the Degree of Cardiac Pathology

Abstract

Chronic Chagasic cardiomyopathy (CCC) is a Neglected Tropical Disease caused by the parasite Trypanosoma cruzi. The pathognomonic findings in symptomatic CCC patients and animal models includes diffuse cardiac fibrosis and inflammation with persistent parasite presence in the heart. This study investigated chemical alterations in different regions of the heart in relation to cardiac pathology indicators to better understand the long-term pathogenesis of this neglected disease. We used data from echocardiography, fibrosis biomarkers, and histopathological analysis to fully evaluate cardiac pathology. Metabolites isolated from the pericardial and endocardial sides of the right ventricular myocardium were analyzed by liquid chromatography tandem mass spectrometry. The endocardial sections contained significantly less cardiac inflammation and fibrosis than the pericardial sections. Cardiac levels of acylcarnitines, phosphocholines, and other metabolites were significantly disrupted in accordance with cardiac fibrosis, inflammation, and serum fibrosis biomarker levels. These findings have potential implications in treatment and monitoring for CCC patients.

Spatial metabolomics identifies localized chemical changes in heart tissue during chronic cardiac Chagas Disease

“…These results concur with independent findings with regards to select acylcarnitines in the serum of CD1 mice chronically infected with T. cruzi strain Brazil (TcI) and to short-chain acylcarnitines and glycerophosphocholines in the heart of BALB/c mice acutely infected with T. cruzi strain Y (TcII) [15]. They also concur with the negative relationship between mid-chain acylcarnitines vs fibrosis and disease progression-associated cytokine PDGF, and the positive relationship between glycerophosphocholines in mass ranges 400-499, 500-599 and over all mass ranges vis-a-vis of inflammation, fibrosis and progression-associated cytokines in the heart of BALB/c mice chronically infected with T. cruzi strain H1 (TcI) [45].…”

“…They also concur with the negative relationship between mid-chain acylcarnitines vs fibrosis and disease progression-associated cytokine PDGF, and the positive relationship between glycerophosphocholines in mass ranges 400–499, 500–599 and over all mass ranges vis-à-vis of inflammation, fibrosis and progression-associated cytokines in the heart of BALB/c mice chronically infected with T . cruzi strain H1 (TcI) [ 45 ].…”

Metabolomic Analysis of Polymicrobial Wound Infections and an Associated Adhesive Bandage

“…The resulting supernatant was transferred to a new plate for LC-MS analysis. We have previously used this method to provide insight into the lipid and metabolic changes associated with different infectious diseases, including parasitic and viral infection (e.g., refs − ; video protocol in ref ), without leading to fewer lipid annotation classes, subclasses or ClassyFire chemical ontology direct parents (comparing ref where extracts were analyzed separately, vs ref where extracts were combined). Biological impact was observed on acylcarnitines and glycerophosphocholines in both cases. , …”

“…On the day of the LC-MS analysis, all samples were resuspended in 120 μL in 1:1 methanol:water prespiked with 2 μM sulfadimethoxine internal standard. This is the recommended resuspension solvent for both aqueous and organic extract by Want et al, 16 20 where extracts were combined). Biological impact was observed on acylcarnitines and glycerophosphocholines in both cases.…”

“…Biological impact was observed on acylcarnitines and glycerophosphocholines in both cases. 20,23 For the optimization run, triplicate samples prepared included a blank, a small piece of the OpSite bandage (approximately 5 mm × 5 mm), 30 μL of a standard mix (0.01 mg/mL sulfadimethoxine, sulfachloropyridazine, sulfamethazine, sulfamethizole, amitriptyline, and 0.02 mg/mL coumarin-314, dissolved in 9:1 H 2 O:MeOH), 30 μL calf serum (Fisher Scientific), the standard mix plus a small piece of the bandage, and the serum plus a small piece of the bandage. The same aqueous and organic extraction method described above was applied to these samples.…”