title: AKT network of genes and impaired myocardial contractility during murine acute Chagasic myocarditis.
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.
authors.affiliation: Division of Infectious Diseases and Departments of Medicine and Immunology, University of Colorado, Denver, Colorado; Department of Epidemiology, Colorado School of Public Health, Denver, Colorado; Department of Pathology, Denver Health, Denver, Colorado andres.henaomartinez@ucdenver.edu.
authors.forename: Andrés F
authors.initials: AF
authors.lastname: Henao-Martínez
authors.affiliation: Division of Infectious Diseases and Departments of Medicine and Immunology, University of Colorado, Denver, Colorado; Department of Epidemiology, Colorado School of Public Health, Denver, Colorado; Department of Pathology, Denver Health, Denver, Colorado.
authors.forename: Anne Hermetet
authors.initials: AH
authors.lastname: Agler
authors.affiliation: Division of Infectious Diseases and Departments of Medicine and Immunology, University of Colorado, Denver, Colorado; Department of Epidemiology, Colorado School of Public Health, Denver, Colorado; Department of Pathology, Denver Health, Denver, Colorado.
authors.forename: Alan M
authors.initials: AM
authors.lastname: Watson
authors.affiliation: Division of Infectious Diseases and Departments of Medicine and Immunology, University of Colorado, Denver, Colorado; Department of Epidemiology, Colorado School of Public Health, Denver, Colorado; Department of Pathology, Denver Health, Denver, Colorado.
authors.forename: Corinne
authors.initials: C
authors.lastname: Hennessy
authors.affiliation: Division of Infectious Diseases and Departments of Medicine and Immunology, University of Colorado, Denver, Colorado; Department of Epidemiology, Colorado School of Public Health, Denver, Colorado; Department of Pathology, Denver Health, Denver, Colorado.
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Davidson
authors.affiliation: Division of Infectious Diseases and Departments of Medicine and Immunology, University of Colorado, Denver, Colorado; Department of Epidemiology, Colorado School of Public Health, Denver, Colorado; Department of Pathology, Denver Health, Denver, Colorado.
authors.forename: Kim
authors.initials: K
authors.lastname: Demos-Davies
authors.affiliation: Division of Infectious Diseases and Departments of Medicine and Immunology, University of Colorado, Denver, Colorado; Department of Epidemiology, Colorado School of Public Health, Denver, Colorado; Department of Pathology, Denver Health, Denver, Colorado.
authors.forename: Timothy A
authors.initials: TA
authors.lastname: McKinsey
authors.affiliation: Division of Infectious Diseases and Departments of Medicine and Immunology, University of Colorado, Denver, Colorado; Department of Epidemiology, Colorado School of Public Health, Denver, Colorado; Department of Pathology, Denver Health, Denver, Colorado.
authors.forename: Michael
authors.initials: M
authors.lastname: Wilson
authors.affiliation: Division of Infectious Diseases and Departments of Medicine and Immunology, University of Colorado, Denver, Colorado; Department of Epidemiology, Colorado School of Public Health, Denver, Colorado; Department of Pathology, Denver Health, Denver, Colorado.
authors.forename: David A
authors.initials: DA
authors.lastname: Schwartz
authors.affiliation: Division of Infectious Diseases and Departments of Medicine and Immunology, University of Colorado, Denver, Colorado; Department of Epidemiology, Colorado School of Public Health, Denver, Colorado; Department of Pathology, Denver Health, Denver, Colorado.
authors.forename: Ivana V
authors.initials: IV
authors.lastname: Yang
mesh_terms: D000818:Animals; D002598:Chagas Cardiomyopathy / Q000378:metabolism* / Q000473:pathology*; D005786:Gene Expression Regulation / Q000502:physiology; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D009200:Myocardial Contraction / Q000235:genetics* / Q000502:physiology; D051057:Proto-Oncogene Proteins c-akt / Q000235:genetics / Q000378:metabolism*; D014349:Trypanosoma cruzi
chemical_list: D051057:Proto-Oncogene Proteins c-akt