Gene expression changes associated with myocarditis and fibrosis in hearts of mice with chronic chagasic cardiomyopathy.
Chronic chagasic cardiomyopathy is a leading cause of heart failure in Latin American countries. About 30% of Trypanosoma cruzi-infected individuals develop this severe symptomatic form of the disease, characterized by intense inflammatory response accompanied by fibrosis in the heart. We performed an extensive microarray analysis of hearts from a mouse model of this disease and identified significant alterations in expression of approximately 12% of the sampled genes. Extensive up-regulations were associated with 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). Our results indicate potentially relevant factors involved in the pathogenesis of the disease that may provide new therapeutic targets in chronic Chagas disease.
Soares
Milena Botelho Pereira
MB
Centro de Pesquisas Gonçalo Moniz, Fundação Oswaldo Cruz, Salvador, Brazil. milena@bahia.fiocruz.br
de Lima
Ricardo Santana
RS
Rocha
Leonardo Lima
LL
Vasconcelos
Juliana Fraga
JF
Rogatto
Silvia Regina
SR
dos Santos
Ricardo Ribeiro
RR
Iacobas
Sanda
S
Goldenberg
Regina Coeli
RC
Iacobas
Dumitru Andrei
DA
Tanowitz
Herbert Bernard
HB
de Carvalho
Antonio Carlos Campos
AC
Spray
David Conover
DC
D000818:Animals; D002598:Chagas Cardiomyopathy / Q000276:immunology* / Q000473:pathology; D016207:Cytokines / Q000096:biosynthesis; D005260:Female; D005355:Fibrosis / Q000276:immunology* / Q000473:pathology; D020869:Gene Expression Profiling; D018836:Inflammation Mediators / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009205:Myocarditis / Q000276:immunology* / Q000473:pathology; D020411:Oligonucleotide Array Sequence Analysis; D014349:Trypanosoma cruzi / Q000276:immunology* / Q000472:pathogenicity*
D016207:Cytokines; D018836:Inflammation Mediators