Microarray analysis of changes in gene expression in a murine model of chronic chagasic cardiomyopathy

Abstract

Chagas' disease, caused by infection with Trypanosoma cruzi, is a major cause of cardiomyopathy in endemic regions. Infection leads to cardiac remodeling associated with congestive heart failure and dilated cardiomyopathy. In order to study the changes in the gene expression profile due to infection, C57BL/6 x 129sv male mice were infected with 1 x 10(3) trypomastigotes of the Brazil strain of T. cruzi. Histopathological examination of the myocardium revealed chronic inflammation, vasculitis and fibrosis 100 days post-infection. Cardiac magnetic resonance imaging revealed a significantly dilated heart compared with uninfected mice. The relative abundance or depletion of myocardial mRNAs was evaluated using high-density microarrays consisting of 27,400 mouse cDNAs, which were hybridized with fluorescent probes generated from mRNAs of T. cruzi infected and uninfected hearts. Differentially expressed genes were sorted according to their normalized expression patterns and functional groups including those involved in transcription, intracellular transport, structure/junction/adhesion or extracellular matrix, signaling, host defense, energetics, metabolism, cell shape and death. The regulated genes are interpreted in the pathogenesis of chagasic heart disease.