Matrix Metalloproteinase 2 and 9 Enzymatic Activities are Selectively Increased in the Myocardium of Chronic Chagas Disease Cardiomyopathy Patients: Role of TIMPs

authors

Baron Monique Andrade
Ferreira Ludmila Rodrigues Pinto
Teixeira Priscila Camillo
Moretti Ana Iochabel Soares
Moretti Soares
Santos Ronaldo Honorato Barros
Frade Amanda Farage
Kuramoto Andréia
Debbas Victor
Benvenuti Luiz Alberto
Gaiotto Fabio Antônio
Bacal Fernando
Pomerantzeff Pablo
Chevillard Christophe
Kalil Jorge
Cunha-Neto Edecio

keywords

Chagas disease
Metalloproteinases
MMP
Heart failure
Cardiac remodeling
Cardiomyopathy
Fibrosis

document type

ART

abstract

Chronic Chagas disease (CCC) is an inflammatory dilated cardiomyopathy with a worse prognosis compared to other cardiomyopathies. We show the expression and activity of Matrix Metalloproteinases (MMP) and of their inhibitors TIMP (tissue inhibitor of metalloproteinases) in myocardial samples of end stage CCC, idiopathic dilated cardiomyopathy (DCM) patients, and from organ donors. Our results showed significantly increased mRNA expression of several MMPs, several TIMPs and EMMPRIN in CCC and DCM samples. MMP-2 and TIMP-2 protein levels were significantly elevated in both sample groups, while MMP-9 protein level was exclusively increased in CCC. MMPs 2 and 9 activities were also exclusively increased in CCC. Results suggest that the balance between proteins that inhibit the MMP-2 and 9 is shifted toward their activation. Inflammation-induced increases in MMP-2 and 9 activity and expression associated with imbalanced TIMP regulation could be related to a more extensive heart remodeling and poorer prognosis in CCC patients.

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