Reversion of gene expression alterations in hearts of mice with chronic chagasic cardiomyopathy after transplantation of bone marrow cells

Milena B P Soares, Ricardo S. Lima, Bruno S F Souza, Juliana F. Vasconcelos, Leonardo L. Rocha, Ricardo Ribeiro Dos Santos, Sanda Iacobas, Regina C. Goldenberg, Michael P. Lisanti, Dumitru A. Iacobas, Herbert B. Tanowitz, David C. Spray, Antonio C. De Campos Carvalho

Research output: Contribution to journalArticle

40 Citations (Scopus)

Abstract

Chronic chagasic cardiomyopathy is a leading cause 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 the transcriptomic recovery induced by BMC therapy by comparing the heart transcriptomes of chagasic mice treated with BMC or saline with control animals. Out of the 9,390 unique genes quantified in all samples, 1,702 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, 96% of the alterations detected in infected hearts were restored to normal levels, although an additional 109 genes were altered by treatment. Transcriptomic recovery, a new measure that considers both restorative and side effects of treatment, was remarkably high (84%). Immunofluorescence and morphometric analyses confirmed the effects of BMC therapy in the pattern of inflammatory-immune response and expression of adhesion molecules. In conclusion, by using large-scale gene profiling for unbiased assessment of therapeutic efficacy we demonstrate immunomodulatory effects of BMC therapy in chronic chagasic cardiomyopathy and identify potentially relevant factors involved in the pathogenesis of the disease that may provide new therapeutic targets.

Original languageEnglish (US)
Pages (from-to)1448-1455
Number of pages8
JournalCell Cycle
Volume10
Issue number9
DOIs
StatePublished - May 1 2011

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Bone Marrow Transplantation
Cardiomyopathies
Bone Marrow Cells
Gene Expression
Cell- and Tissue-Based Therapy
Fibrosis
Genes
Inflammation
Chagas Disease
Therapeutics
Transcriptome
Fluorescent Antibody Technique
Mitochondria
Chronic Disease
Down-Regulation
Heart Failure

Keywords

  • Cardiomyopathy
  • Cell transplantation
  • Chagas disease
  • Fibrosis
  • Inflammation
  • Microarray
  • Trypanosoma cruzi

ASJC Scopus subject areas

  • Cell Biology
  • Molecular Biology
  • Developmental Biology

Cite this

Soares, M. B. P., Lima, R. S., Souza, B. S. F., Vasconcelos, J. F., Rocha, L. L., Dos Santos, R. R., ... De Campos Carvalho, A. C. (2011). Reversion of gene expression alterations in hearts of mice with chronic chagasic cardiomyopathy after transplantation of bone marrow cells. Cell Cycle, 10(9), 1448-1455. https://doi.org/10.4161/cc.10.9.15487

Reversion of gene expression alterations in hearts of mice with chronic chagasic cardiomyopathy after transplantation of bone marrow cells. / Soares, Milena B P; Lima, Ricardo S.; Souza, Bruno S F; Vasconcelos, Juliana F.; Rocha, Leonardo L.; Dos Santos, Ricardo Ribeiro; Iacobas, Sanda; Goldenberg, Regina C.; Lisanti, Michael P.; Iacobas, Dumitru A.; Tanowitz, Herbert B.; Spray, David C.; De Campos Carvalho, Antonio C.

In: Cell Cycle, Vol. 10, No. 9, 01.05.2011, p. 1448-1455.

Research output: Contribution to journalArticle

Soares, MBP, Lima, RS, Souza, BSF, Vasconcelos, JF, Rocha, LL, Dos Santos, RR, Iacobas, S, Goldenberg, RC, Lisanti, MP, Iacobas, DA, Tanowitz, HB, Spray, DC & De Campos Carvalho, AC 2011, 'Reversion of gene expression alterations in hearts of mice with chronic chagasic cardiomyopathy after transplantation of bone marrow cells', Cell Cycle, vol. 10, no. 9, pp. 1448-1455. https://doi.org/10.4161/cc.10.9.15487
Soares, Milena B P ; Lima, Ricardo S. ; Souza, Bruno S F ; Vasconcelos, Juliana F. ; Rocha, Leonardo L. ; Dos Santos, Ricardo Ribeiro ; Iacobas, Sanda ; Goldenberg, Regina C. ; Lisanti, Michael P. ; Iacobas, Dumitru A. ; Tanowitz, Herbert B. ; Spray, David C. ; De Campos Carvalho, Antonio C. / Reversion of gene expression alterations in hearts of mice with chronic chagasic cardiomyopathy after transplantation of bone marrow cells. In: Cell Cycle. 2011 ; Vol. 10, No. 9. pp. 1448-1455.
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AU - Souza, Bruno S F

AU - Vasconcelos, Juliana F.

AU - Rocha, Leonardo L.

AU - Dos Santos, Ricardo Ribeiro

AU - Iacobas, Sanda

AU - Goldenberg, Regina C.

AU - Lisanti, Michael P.

AU - Iacobas, Dumitru A.

AU - Tanowitz, Herbert B.

AU - Spray, David C.

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