title: Fibrosis and hypertrophy induced by Trypanosoma cruzi in a three-dimensional cardiomyocyte-culture system.
abstract: Cardiac damages caused by in vivo infection with Trypanosoma cruzi are still not fully clarified. Here we describe for the first time an in vitro model of fibrosis, hypertrophy, and remodeling induced by T. cruzi in cardiomyocyte spheroids (cardiac microtissues). In this new 3-dimensional system, cardiac spheroids showed spontaneous contractility, with typical cardiac morphology and production of extracellular matrix components. There were 4- and 6-fold increases, respectively, in the area and the volume of T. cruzi-infected cardiomyocytes and whole microtissues, together with a 50% reduction of the cell population. Immunofluorescence showed increased expression of fibronectin, collagen IV, and laminin in the microtissues 144 h after infection. T. cruzi infection induced an increase in both the cellular area and the extracellular matrix components in cardiac spheroids, which contributed to an increase in total microtissue volume, making this a powerful 3-dimensional in vitro model for the study of cardiac-tissue hypertrophy, fibrosis, and remodeling.
authors.affiliation: Laboratório de Farmacologia Neurocardiovascular, Instituto Oswaldo Cruz/Fiocruz, Rio de Janeiro, RJ, Brazil. largarz@ioc.fiocruz.br
authors.forename: Luciana Ribeiro
authors.initials: LR
authors.lastname: Garzoni
authors.forename: Daniel
authors.initials: D
authors.lastname: Adesse
authors.forename: Maurilio José
authors.initials: MJ
authors.lastname: Soares
authors.forename: Maria Isabel Doria
authors.initials: MI
authors.lastname: Rossi
authors.forename: Radovan
authors.initials: R
authors.lastname: Borojevic
authors.forename: Maria de Nazareth Leal
authors.initials: Mde N
authors.lastname: de Meirelles
mesh_terms: D000818:Animals; D002598:Chagas Cardiomyopathy / Q000469:parasitology* / Q000473:pathology*; D002522:Chlorocebus aethiops; D005109:Extracellular Matrix / Q000469:parasitology / Q000502:physiology; D005355:Fibrosis / Q000469:parasitology; D051379:Mice; D032383:Myocytes, Cardiac / Q000469:parasitology* / Q000473:pathology*; D014349:Trypanosoma cruzi / Q000502:physiology*; D014709:Vero Cells