AKT Network of Genes and Impaired Myocardial Contractility During Murine Acute Chagasic Myocarditis

Abstract

Abstract. Chagasic disease is associated with high morbidity in Latin America. Acute Chagasic myocarditis is consistently found in acute infections, but little is known about its contribution to chronic cardiomyopathy. The aim of the study was to phenotypically characterize two strains of mice with differential Chagas infection susceptibility and correlate strain myocarditis phenotypes with heart tissue gene expression. C57BL/6J and Balb/c mice were injected intraperitoneally with 0 or 150-200 tissue-derived trypomastigotes (Tulahuen strain). Echocardiograms, brain natriuretic peptide, and troponin were measured. Heart tissue was harvested for histopathological analysis and gene expression profiling on microarrays. Genes differently expressed between infected Balb/c and C57BL/6J mice were identified. Echocardiograms showed differences in Balb/c versus C57BL/6J infected mice in heart rate (413 versus 476 beats per minute; P = 0.0001), stroke volume (31.9 ± 9.3 versus 39.2 ± 5.5 μL; P = 0.03), and cardiac output (13.1 ± 3.5 versus 18.7 ± 3.2 μL/min; P = 0.002). Gene expression at 4 weeks analysis showed 32 statistically significant (q value 0.05) differentially expressed genes between infected Balb/c and C57BL/6J mice that were enriched for genes related to the protein kinase B (AKT) pathway. These specific phenotypic features of cardiac response during acute Chagasic myocarditis may, in part, be related to host AKT network regulation.

Moderate Treadmill Exercise Training Improves Cardiovascular and Nitrergic Response and Resistance to Trypanosoma cruzi Infection in Mice

“…Clinically, T. cruzi infection causes acute myocarditis, followed by chronic cardiomyopathy, in humans and experimental models (Scharfstein and Andrade, 2011 ; Henao-Martínez et al, 2015 ). Most infected individuals remain asymptomatic for several years.…”

Murine heart gene expression during acute Chagasic myocarditis

“…This data analysis was published recently [4] . This correlation showed that a network of genes, especially the AKT gene, could be associated with decreased heart muscle strength (contractility) during the initial infection [5] . This may be proven to be important to further identify potential host genes involved with an early worse cardiac response during the acute infection which could also be associated with the later development of chronic Chagas cardiac disease.…”

“…These specific responses to organ injury might be in part responsible of different phenotypes during the acute infection and could correlate with chronic organ damage. The study evaluated differences in cardiac contractility among the two strains during acute infection [5] . Network of protein kinase B (AKT), NCAM1, HLA-DRA, and ubiquitin C genes are differently expressed among the two strains of mice during acute myocardial Chagas infection and may be responsible for the contractility differences seen among the mice strains.…”

“…Additionally human studies of chronic Chagasic cardiomyopathy may be prove useful evaluating the prognostic capacity of these molecules as potential biomarkers. Other genes are also differentially expressed and could also be potentially studied [5] .…”