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AKT network of genes and impaired myocardial contractility during murine acute chagasic myocarditis

ABSTRACT: Rationale: 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. Methods: 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 were identified Results: Echocardiograms demonstrated differences in heart rate in Balb/c vs. C57BL/6J infected mice: 413 vs. 476 bpm, (p=0.0001), stroke volume: 31.9 ± 9.3 vs. 39.2 ± 5.5 µl (p=0.03); and cardiac output: 13.1 ± 3.5 vs. 18.7 ± 3.2 µl/min (p=0.002). Gene expression at 4 weeks analysis demonstrated 32 statistically significant (q-value < 0.05) differentially expressed genes between infected Balb/c and C57BL/6J which were enriched for genes related to protein kinase B (AKT) pathway

ORGANISM(S): Mus musculus

PROVIDER: GSE63847 | GEO | 2014/12/05

SECONDARY ACCESSION(S): PRJNA269252

REPOSITORIES: GEO

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AKT network of genes and impaired myocardial contractility during murine acute chagasic myocarditis

Project description:Rationale: 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. Methods: 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 were identified Results: Echocardiograms demonstrated differences in heart rate in Balb/c vs. C57BL/6J infected mice: 413 vs. 476 bpm, (p=0.0001), stroke volume: 31.9 ± 9.3 vs. 39.2 ± 5.5 µl (p=0.03); and cardiac output: 13.1 ± 3.5 vs. 18.7 ± 3.2 µl/min (p=0.002). Gene expression at 4 weeks analysis demonstrated 32 statistically significant (q-value < 0.05) differentially expressed genes between infected Balb/c and C57BL/6J which were enriched for genes related to protein kinase B (AKT) pathway 8 Balb/c mice and 8 C57BL/6J mice were infected and 8 Balb/c and 8 C57BL/6J were used as controls. 6 mice per group were used for gene expression analysis.

2014-12-05 | E-GEOD-63847 | biostudies-arrayexpress

QTL for renal and cardiac function during Angiotensin II and high-sodium treatment of a backcross between C57BL/6J-to-Balb/CJ-F1 and Balb/CJ

Project description:Balb/CJ mice develop heart failure and quickly decompensate during combination treatment with Angiotensin II and high-sodium diet, while C57BL/6J mice do not. Balb/CJ show a predominantly diastolic heart failure, signs of increased pulmonary pressure, relative sodium and fluid retention, peripheral edema and decompensate with anuria in a cardiorenal syndrome. A F1 cross between the strains have a similar phenotype as C57BL/6J, i.e. is protected. The present study used a second generation backcross of the F1-generation to Balb/CJ and pheotyped a wide variety of renal and circulatory and cardiac traits, identifying 9 new QTL.

2019-06-13 | E-MTAB-8047 | biostudies-arrayexpress

Therapy with bone marrow cells recovers gene expression alterations in hearts of mice with chronic chagasic cardiomyopathy

Project description:Chronic chagasic cardiomyopathy is one of the leading causes of heart failure in Latin American countries, being associated with intense inflammatory response and fibrosis. We have previously shown that bone marrow mononuclear cell (BMC) transplantation improves inflammation, fibrosis and ventricular diameter in hearts of mice with chronic Chagas’ disease. Here we investigated alterations of gene expression in the hearts of chronic chagasic mice submitted or not to BMC therapy. C57Bl/6 mice chronically infected with T. cruzi (6 months) were transplanted with BMC or saline i.v. and sacrificed 2 months later. RNA was extracted from the hearts of normal controls, chagasic and BMC transplanted mice and microarray analysis was performed using MO30k oligonucleotide arrays. Out of the 9390 unigenes quantified in all samples, 1702 had their expression altered in chronic chagasic hearts compared to those of normal mice. Major categories of significantly upregulated genes were related to inflammation, fibrosis and immune responses, while genes involved in mitochondrion function were downregulated. When BMC-treated chagasic hearts were compared to infected mice, 1631 (96%) of the alterations detected in infected hearts were not found, although an additional 109 genes were altered by treatment, indicating a remarkable 84% transcriptomic recovery. Immunofluorescence and morphometric analyses confirmed the effects of BMC therapy in the pattern of inflammatory-immune response and expression of adhesion molecules. Our results demonstrate important immunomodulatory effects of BMC therapy in chagasic cardiomyopathy and indicate potentially relevant factors involved in the pathogenesis of the disease that may provide new therapeutic targets.

2010-09-17 | GSE24088 | GEO

Expression data from mouse intestine: C57Bl/6 MTHFR+/- vs BALB/c MTHFR+/-

Project description:Previous studies in our laboratory have shown that low folate diet (control diet with 2mg folate/kg, low folate diet with 0.3mg folate/kg) can induce intestinal tumors in BALB/c mice. In addition, we reported that C57Bl/6J mice did not form tumors under the same conditions. We used microarrays to identify the genetic differences between BALB/c and C57Bl/6J mice that promote tumorigenesis in BALB/c mice.

2013-04-09 | GSE34010 | GEO

Gene expression changes associated with myocarditis and fibrosis in hearts of mice with chronic chagasic cardiomyopathy

Project description:Chronic chagasic cardiomyopathy is a leading cause of heart failure in Latin American countries. About 30% of Trypanosoma cruzi-infected individuals develop this severe symptomatic form of the disease, characterized by intense inflammatory response accompanied by fibrosis deposition in the heart. We performed a microarray analysis of a mouse model of this disease and identified >5% alterations of gene expression in the heart. Most of the upregulations were associated with immune-inflammatory responses (chemokines, adhesion molecules, cathepsins and MHC molecules) and fibrosis deposition (extracellular matrix components, lysyl oxidase and Timp1). Our results indicate potentially relevant factors involved in the pathogenesis of the disease that may provide new therapeutic targets in chronic Chagasâ disease. The heart transcriptomes of 4 age-mached Trypanosoma cruzi-infected and 4 control C57Bl/6 mice were profiled and compared using Duke Mouse 30k Oligonucleotide Arrays (Operon V3.0.1) hybridized in the "multiple yellow" strategy described in Iacobas et al, Biochem Biophys Res Commun. 2006 349(1):329-38.

2010-05-15 | E-GEOD-17363 | biostudies-arrayexpress

Quantitative proteome analysis of liver in acute cardiac rejection in mice

Project description:In order to study the changes of liver protein level in mice with acute cardiac rejection, we established a mouse model of ectopic heart transplantation. According to the matching relationship between recipient and donor, they were divided into the following two groups: allograft group (ALLO), BALB/ C hearts were transplanted into C57BL/6J recipients with complete mismatch of major histocompatibility complex; In the syngeneic transplantation group (ISO), C57BL/6J hearts were transplanted into MHC-matched C57BL/6J recipients. On day 6 after mouse heart transplantation, livers were obtained from recipient mice in the allograft group (n = 3) and from recipient mice in the syngeneic (ISO) group (n = 3). A series of techniques such as protein extraction, enzyme digestion, TMT labeling, HPLC classification, liquid chromatography-mass spectrometry tandem analysis, database search and bioinformation analysis were used to study the quantitative proteome of samples.

2022-09-05 | PXD044536 | iProX

ACAA2 genome-binding patterns before and after transverse aortic constriction in C57Bl/6J mice on different diets [ACAA2]

Project description:Acetyl-CoA acyltransferace 2 (ACAA2) associates with chromatin at promoter sites in the heart of C57Bl/6J mice. A high-fat vs. low-fat diet reduces it promoter abundance, whereas, transverse aortic constriction (TAC) increases it slight.

2021-05-11 | GSE165284 | GEO

The study of sex differences during the innate immune response against coxsackievirus B3 (CVB3)-induced myocarditis (12hr post infection)

Project description:Men are at an increased risk of dying from heart failure caused by inflammatory heart diseases such as atherosclerosis, myocarditis and dilated cardiomyopathy (DCM). We previously showed that macrophages in the spleen are phenotypically distinct in male compared to female mice at 12 hours (h) after infection. This innate immune profile mirrors and predicts the cardiac immune response during acute myocarditis. Groups consisted of Infected Males, Infected Females, Uninfected Males and Uninfected females. There are 5 mice per group. A total of 20 samples were analyzed in this experiment.

2011-01-14 | E-GEOD-26630 | biostudies-arrayexpress

Transcriptome analysis of lungs from six different mouse strains after infection with highly pathogenic H5N1 influenza A virus [set 2]

Project description:Susceptible (DBA/2J, 129/SvImJ, A/J) and Resistant (SM/J, C57BL/6J, Balb/cJ) mouse strain were inoculated with a highly pathogenic H5N1 influenza A virus (A/Hong Kong/213/2003) for 72 hours or not infected (control animals). Differences in expression were analyzed and used to identify candidate genes and pathways that contributed to the difference in H5N1 pathogenesis in these two groups of mice.

2015-01-09 | GSE64799 | GEO

Wildtype (wt) mouse cone transcriptome change with Txnip treatment

Project description:Purpose: To identifiy mRNA changes in wt cone photoreceptors with Txnip overexpression treatment, which improved retinitis pigmentosa (RP) cone survival and visual acuity. Methods: two wt mouse strains, BALB/c and C57BL/6J were injected with AAV-Txnip or AAV-H2BGFP control subretinally at P0. Retinas were dissected out at P21 for BALB/c and P35 for C57BL/6J. 1,000 H2BGFP labeled cones per retina sample were FACS sorted out, and subject for RNA-sequencing. Results: only ~70 genes in P21 BALB/c and 1 genes in C57BL/6J were found differentially expressed with Txnip treatment. Only 1 genes (i.e. Txnip) were in commonly upregulated between the two lists. Conclusions: Txnip seems to be not changing RNA expression much in wt cones. Instead, its major function to rescue RP cones may lay in protein-protein interactions.

2021-03-15 | GSE168503 | GEO

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