Gene Expression Changes Associated with Myocarditis and Fibrosis in Hearts of Mice with Chronic Chagasic Cardiomyopathy

Soares, Milena Botelho Pereira; Lima, Ricardo Santana de; Rocha, Leonardo Lima; Vasconcelos, Juliana Fraga; Rogatto, Sílvia Regina; Santos, Ricardo Ribeiro dos; Iacobaş, Sanda; Goldenberg, Regina Coeli dos Santos; Iacobaş, Dumitru A.; Tanowitz, Herbert B.; Carvalho, Antônio Carlos Campos de; Spray, David C.

doi:10.1086/653481

Cited by 60 publications

(72 citation statements)

References 48 publications

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“…There is evidence that activation of ERK 1/2 and expression of LOX are involved in the effects of PDGF-BB and/or TGF-β1 on cellular migration and proliferation of endothelial and smooth muscle cells during the process of vascular remodeling (Qi et al, 2011). Cardiomyopathy has been created in mice by infection of T. Cruse, resulting in the up-regulation of LOX, other ECM-related genes, tissue inhibitor of metalloproteinase (TIMP-1), and TGF-β (Soares et al, 2010). In cardiac fibroblasts, Rac1 GTPase was shown to mediate up-regulation of fibronectin via LOX and connective tissue growth factor (CTGF).…”

Section: Introduction and Molecular Biology Of Loxmentioning

confidence: 99%

Lysyl Oxidase: From Basic Science to Future Cancer Treatment

Nishioka

Eustace

West

2012

Cell Struct. Funct.

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ABSTRACT. In this mini-review, we discuss the physiological and pathological roles of lysyl oxidase (LOX) and its family, LOX-like proteins (LOXL), in relation to prognosis of major cancers. The number of reports on LOX family is numerous. We have decided to review the articles that were recently published (i.e. past 5 years). Experimental techniques in molecular biology have advanced surprisingly in the past decade. Accordingly, the results of the studies are more reliable. Most studies reached the same conclusion; a higher LOX-or LOXLexpression is associated with a poor prognosis. Molecular experiments have already started aiming for clinical application, and the results are encouraging. Suppressing LOX or LOXL activities resulted in lower cell motility in collagen gel and, moreover, succeeded in reducing metastases in mice. LOX family members were originally recognized as molecules that cross-link collagen fibers in the extracellular matrix. Recent studies demonstrated that they are also involved in a phenomenon called Epithelial Mesenchymal Transition (EMT). This may affect cell movement and cancer cell invasiveness. LOX and LOXL2 are regulated by hypoxia, a major factor in the failure of cancer treatment. Here we discuss the molecular biology of the LOX family in relation to its role in tumor biology.

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Section: Introduction and Molecular Biology Of Loxmentioning

confidence: 99%

Lysyl Oxidase: From Basic Science to Future Cancer Treatment

Nishioka

Eustace

West

2012

Cell Struct. Funct.

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“…24,25 In contrast, chronic infection is associated with up-regulation of immune inflammatory responses (chemokines, adhesion molecules, cathepsins, and major histocompatibility complex molecules) and fibrosis (extracellular matrix components, lysyl oxidase, and tissue inhibitor of metalloproteinase 1). 26 There are several limitations to our study. The echocardiogram and heart histology findings at 4 weeks may reflect a survival effect, particularly among Balb/c mice.…”

Section: Discussionmentioning

confidence: 94%

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

Henao‐Martínez

Agler

Watson

et al. 2015

The American Society of Tropical Medicine and Hygiene

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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.

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“…Over the past decade there have been a number of microarray studies by our laboratory group and others examining the consequences of T. cruzi infection on murine heart, [26][27][28] cultured cardiac myocytes, 29 myoblasts, 30 was not regulated as a result of either infection with T. cruzi treatment with 50 nM IBOP, a TP receptor against (Fig. 2B).…”

Section: Discussionmentioning

confidence: 99%