Cell Death and Serum Markers of Collagen Metabolism during Cardiac Remodeling in Cavia porcellus Experimentally Infected with Trypanosoma cruzi
| Autor: | Henry Paico, Robert H. Gilman, Noelia Angulo, Caryn Bern, Verónica Yauri, Fredy Ccopa, Yagahira E. Castro-Sesquen |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2013 |
| Předmět: |
Chagas Cardiomyopathy
Pathology Chagas Cardiomyopathy pathology Necrosis Cardiac fibrosis Antibodies Protozoan 030204 cardiovascular system & hematology Cardiovascular Myocardium pathology 0302 clinical medicine Fibrosis Molecular Cell Biology Immunoglobulin blood Collagen metabolism 0303 health sciences Cell Death lcsh:Public aspects of medicine Animal Models Immunohistochemistry Extracellular Matrix 3. Good health Infectious Diseases Connective Tissue Medicine Female Collagen medicine.symptom purl.org/pe-repo/ocde/ford#3.03.06 [https] Research Article medicine.medical_specialty Programmed cell death lcsh:Arctic medicine. Tropical medicine lcsh:RC955-962 Trypanosoma cruzi Immunology Guinea Pigs Inflammation Biology 03 medical and health sciences Model Organisms Parasitic Diseases medicine Animals Chagas Disease 030304 developmental biology Heart Failure Myocardium Public Health Environmental and Occupational Health lcsh:RA1-1270 medicine.disease biology.organism_classification Disease Models Animal Terminal deoxynucleotidyl transferase Trypanosoma cruzi pathogenicity Apoptosis Antibodies Protozoan blood Immunoglobulin G Infectious Disease Modeling Biomarkers |
| Zdroj: | PLoS Neglected Tropical Diseases PLoS Neglected Tropical Diseases, Vol 7, Iss 2, p e1996 (2013) |
| Popis: | 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. Author Summary Chronic Chagas heart disease (CHHD) caused by the infection with the parasite Trypanosoma cruzi is the most important infectious heart disease in the world. The typical manifestations are dilated cardiomyopathy and congestive heart failure; they result from death of cardiomyocytes and their replacement by collagen. Knowing the mechanisms of cardiomyocyte death is important for the development of therapies that prevent them. 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. We observed apoptosis of lymphocytes, cardiomyocytes, endothelial cells and epicardial adipose tissue in cardiac tissue of infected guinea pigs. The increase of serum levels of collagen precursors PICP and PIIINP were associated with cardiac fibrosis. Areas of inflammation and apoptosis of epicardial adipose tissue were associated with cardiac pathology, which suggests the importance of epicardial adipose tissue in CCHD. These results show that apoptosis is an important characteristic of cardiac cell death during CCHD and serum levels of PICP and PIIINP could be used as biomarkers of cardiac fibrosis. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|