Assessment of syndecan-4 expression in the hearts of Trypanosoma cruzi -infected mice and human subjects with chronic Chagas disease cardiomyopathy

Surgical and Experimental Pathology

Diogo Crispim Nascimento Portella¹  Ticiana Ferreira Larocca¹  do¹  o David de Souza Neto¹  Milena Botelho Pereira Soares²  Fabio Rocha Fernandes Tavora²  Juliana Fraga Vasconcelos²  Carolina Thé²  Joã³  Daniela Nascimento Silva³  Macê³  Bruno Solano de Freitas Souza⁴  Carine Machado Azevedo⁴  Ricardo Ribeiro dos Santos⁴  Washington Luis Conrado dos Santos⁴ 

[1] Center for Biotechnology and Cell Therapy, SãGonçalo Moniz Research Center, FIOCRUZ, Salvador, Brazil;o Rafael Hospital, Salvador, Brazil

关键词: Syndecan-4;    Chagas disease;    Cardiomyopathy;   

DOI  :  10.1186/s42047-018-0012-9

学科分类：生理学与病理学

来源: Springer

【 摘 要 】

Chronic Chagas cardiomyopathy (CCC) is characterized by the presence of a multifocal inflammatory response and myocardial damage, leading to fibrosis, arrhythmias and ventricular dysfunction. The expression of syndecan-4, a transmembrane proteoglycan, was previously found to be increased in the hearts of mice chronically infected with Trypanosoma cruzi. The possible involvement of syndecan-4 in the disease pathogenesis, however, remains unknown. Here we evaluated the pattern of expression of syndecan-4 in the heart tissue of T. cruzi infected mice and subjects with Chagas cardiomyopathy, correlating with the degree of inflammation and fibrosis. The expression of syndecan-4 was evaluated by immunofluorescence and RT-qPCR in the hearts of C57Bl/6 mice at different time points after infection with the Colombian strain of T. cruzi. Immunostainings for syndecan-4 were performed in heart samples obtained from CCC patients and other etiologies of heart failure. The number of infiltrating inflammatory cells and area of fibrosis were also evaluated and quantified. In the experimental model, the number of infiltrating inflammatory cells and fibrosis area in the hearts progressively increased after the acute phase of infection, while syndecan-4 expression remained elevated in similar levels in both the acute and chronic phases. Confocal microscopy analysis demonstrated the localization of syndecan-4 expression in blood vessels, co-localized with α-SMA, a marker for vascular smooth muscle cells (VSMCs). Confocal microscopy analysis of human hearts samples showed a similar pattern of syndecan-4 expression in blood vessels. No correlation between syndecan-4 expression and inflammation or fibrosis was found in the hearts from subjects with CCC. We also compared the expression of syndecan-4 evaluated in subjects with CCC, idiopathic dilated cardiomyopathy and ischemic cardiomyopathy. No differences in the number of syndecan-4 positive vessels/mm2 were found comparing the three groups (P = 0.466), whereas CCC patients presented a higher number of infiltrating inflammatory cells, compared to the other etiologies of heart failure. Additionally, no correlation between syndecan-4 and fibrosis or numbers of inflammatory cells was found. Syndecan-4 is expressed in the heart during the acute and chronic phases of Chagas disease, in association with VSMCs, independently of the degree of myocardial fibrosis or the number of infiltrating inflammatory cells.

【 授权许可】

CC BY