Granulocyte colony-stimulating factor partially repairs the damage provoked by Trypanosoma cruzi in murine myocardium

Mariela Natacha González, Nilay Dey, Nisha Jain Garg, Miriam Postan

Research output: Contribution to journalArticle

7 Scopus citations

Abstract

Background The hallmark of Trypanosoma cruzi infection is cardiomyopathy that leads to end-stage heart failure. We investigated whether G-CSF, known to induce heart tissue repair by bone marrow stem cell mobilization, ameliorates T. cruzi-induced myocarditis. Methods and results T. cruzi-infected C3H/He mice were treated with G-CSF and monitored for parasite burden, BMSC mobilization, cytokine profile and cardiac remodeling. G-CSF increased the expression of CXCR4, CD34, and c-Kit, indicating mobilization and migration of BMSC, some of which differentiated to cardiomyocytes as evidenced by increased levels of GATA4+/MEF2C+ cells and desmin expression in chagasic hearts. G-CSF enhanced a mixed cytokine response (IL-10 + TGF-β > IFN-γ + TNF-α > IL-4) associated with increased heart inflammation and no beneficial effect on parasite control. Further, G-CSF controlled T. cruzi-induced extracellular-matrix alterations of collagens (Col I and Col llI), hydroxyproline, and glycosaminoglycan contents and promoted compensatory cardiac remodeling; however, these responses were not sufficient to control T. cruzi-induced cardiomyocyte atrophy. Benznidazole treatment prior to G-CSF resulted in the control of parasitism and parasite-induced inflammation, and subsequently, G-CSF was effective in executing the tissue repair, as evidenced by extracellular-matrix homeostasis and normalization of cardiomyocyte size in chagasic hearts. Conclusions G-CSF treatment after T. cruzi infection enhanced migration and homing of BMSC, some of which differentiated to cardiomyocytes. Yet, G-CSF promoted a mixed (Treg > Th1 > Th2) immune response that contributed to persistent inflammation and limited improvement in cardiac homeostasis. Combinatorial therapy (BZ → G-CSF) was beneficial in arresting inflammatory processes and tissue damage in chagasic hearts.

Original languageEnglish (US)
Pages (from-to)2567-2574
Number of pages8
JournalInternational Journal of Cardiology
Volume168
Issue number3
DOIs
StatePublished - Oct 3 2013

Keywords

  • Cardiac repair
  • Chagas disease
  • G-CSF
  • Stem cell
  • Trypanosoma cruzi

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine

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