Abstract
We studied cell death by apoptosis and necrosis in cardiac remodeling produced by Trypanosoma cruzi infection. In addition, we evaluated collagen I, III, IV (CI, CIII and CIV) deposition in cardiac tissue, and their relationship with serum levels of procollagen type I carboxy-terminal propeptide (PICP) and procollagen type III amino-terminal propeptide (PIIINP). Eight infected and two uninfected guinea pigs were necropsied at seven time points up to one year post-infection. Cell death by necrosis and apoptosis was determined by histopathological observation and terminal deoxynucleotidyl transferase dUTP nick end labeling, respectively. Deposition of cardiac collagen types was determined by immunohistochemistry and serum levels of PICP, PIIINP, and anti-T. cruzi IgG1 and IgG2 by ELISA. IgG2 (Th1 response) predominated throughout the course of infection; IgG1 (Th2 response) was detected during the chronic phase. Cardiac cell death by necrosis predominated over apoptosis during the acute phase; during the chronic phase, both apoptosis and necrosis were observed in cardiac cells. Apoptosis was also observed in lymphocytes, endothelial cells and epicardial adipose tissue, especially in the chronic phase. Cardiac levels of CI, CIII, CIV increased progressively, but the highest levels were seen in the chronic phase and were primarily due to increase in CIII and CIV. High serum levels of PICP and PIIINP were observed throughout the infection, and increased levels of both biomarkers were associated with cardiac fibrosis (p = 0.002 and p = 0.038, respectively). These results confirm the role of apoptosis in cell loss mainly during the chronic phase and the utility of PICP and PIIINP as biomarkers of fibrosis in cardiac remodeling during T. cruzi infection.
Highlights
Chagas disease, a parasitic infection caused by Trypanosoma cruzi, remains a major public health problem in Central and South America with 8 to 10 million people infected [1]
The contribution of apoptosis in cardiomyocyte death was evaluated in the guinea pig model of T. cruzi infection, and the detection of serum levels of collagen precursors were evaluated as biomarkers of cardiac fibrosis
The increase of serum levels of collagen precursors procollagen type I carboxy-terminal propeptide (PICP) and procollagen type III amino-terminal propeptide (PIIINP) were associated with cardiac fibrosis
Summary
A parasitic infection caused by Trypanosoma cruzi, remains a major public health problem in Central and South America with 8 to 10 million people infected [1]. Chronic Chagas heart disease (CCHD), the major clinical consequence, is the most important infectious heart disease in the world, with an estimated 50,000 attributable deaths per year [2]. Sudden death may result from arrhythmias, heart block or emboli; patients with advanced cardiomyopathy may die of intractable heart failure [4]. These clinical manifestations result from sequential changes that occur at the cellular level, including lengthening of cardiomyocytes, rearrangement within the myocardial matrix, and death of cardiomyocytes and their replacement by connective tissue; all these changes are part of so-called cardiac remodeling [9]
Sign-in/Register to view highlights & summary 
Published Version (
Free)
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call