Tissue Inhibitor of Metalloproteinase-1 Is Increased in Chagasic Cardiomyopathy

Abstract

Chagas disease (CD) mainly conveys stroke risk through structural cardiac disease. However, stroke and cognitive impairment are seen in CD independently of cardiac disease severity. Chronic inflammation may be an explanation for this association, because inflammation plays an important role in the pathogenesis of acute ischemic stroke and dementia. In the present study, we selected five candidate biomarkers for Chagas disease: interleukin-6, membrane metalloproteinase-9, tissue inhibitor of metalloproteinase-1 (TIMP1), orosomucoid, and neprilysin. We sought to determine if mean levels of proinflammatory biomarkers are higher in patients with heart failure (HF) associated with Chagas disease when compared with other etiologies of HF. Patients were consecutively enrolled from subspecialty HF outpatient clinics at two university-based hospitals. Serum biomarker levels from blood samples were analyzed by ELISA. Severity of HF on echocardiography was worse in non-CD when compared with CD patients. No significant difference was observed in the levels of candidate biomarkers between the CD and non-CD groups. We found a significantly 2.2 ng/mL higher level of TIMP1 in CD when compared with non-CD patients with HF after adjustment for age and gender (95% confidence interval = 0.1 to 4.5, P = 0.037). In patients with heart failure, serum TIMP1 is increased in Chagas patients despite a lower myocardial disease severity on echocardiography when compared with non-Chagas patients. TIMP1 is probably one of multiple mediators of inflammatory injury.

Figure 1.

Serum biomarker levels in patients with heart failure (Chagas and non-Chagas etiologies). Dots represent individual biomarker levels, while horizontal black lines represent the 25th, 50th, and 75th percentiles. (A) Matrix metalloproteinase-9 (MMP9) and tissue inhibitor of metalloproteinase-1 (TIMP1). (B) Neprilysin. (C) Orosomucoid. (D) Interleukin-6 (IL6). The only significant association was between Chagas disease and higher TIMP1 levels (P = 0.037); see Table 2.