首页 | 本学科首页   官方微博 | 高级检索  
   检索      


TNF blockade aggravates experimental chronic Chagas disease cardiomyopathy
Authors:Bilate Angelina M B  Salemi Vera M  Ramires Felix J  de Brito Thales  Russo Momtchilo  Fonseca Simone G  Faé Kellen C  Martins Daniel G  Silva Ana Maria  Mady Charles  Kalil Jorge  Cunha-Neto Edecio
Institution:1. Center for Drug Delivery and Nanomedicine, College of Pharmacy, University of Nebraska Medical, Omaha, NE, USA;2. Department of Pharmaceutical Sciences, College of Pharmacy, University of Nebraska Medical, Omaha, NE, USA;3. Donald P. Shiley BioScience Center, San Diego State University, San Diego, CA, USA;1. Department of Neurology and Neurosurgery, Universidade Federal de São Paulo (UNIFESP), São Paulo, Brazil;2. Department of Physiology and Biophysics, Institute of Biomedical Science, Universidade de São Paulo, São Paulo, SP, Brazil
Abstract:Chronic Chagas disease cardiomyopathy (CCC), caused by Trypanosoma cruzi, is an inflammatory dilated cardiomyopathy associated with increased circulating levels of TNF-alpha. We investigate whether TNF blockade with Etanercept during the chronic phase of T. cruzi infection could attenuate experimental CCC development. The effect of Etanercept was evaluated after 11 months of T. cruzi infection on survival, parasitism, left ventricular function, intensity of myocarditis, fibrosis, and left ventricular mRNA expression of cytokines and TNF-alpha-induced genes. Left ventricular function was significantly reduced in treated animals as compared to infected untreated animals. Blood and cardiac parasitism as well as survival rate were not altered with Etanercept treatment. Inflammatory infiltrates were located predominantly in the subendocardic region in treated animals, whereas in untreated animals inflammation was scattered throughout the myocardium. Left ventricular mRNA IL-10 expression was significantly higher, and iNOS, significantly lower in treated than in untreated animals. mRNA expression of TNF-alpha, IFN-gamma, TGF-beta, A20 and ANP was similar in both groups. Our results suggest that TNF-alpha/LT-alpha blockade with Etanercept enhances left ventricular dysfunction in T. cruzi-induced chronic cardiomyopathy and the absence of TNF signaling may be deleterious to the failing heart in Chagas disease cardiomyopathy.
Keywords:
本文献已被 ScienceDirect PubMed 等数据库收录!
设为首页 | 免责声明 | 关于勤云 | 加入收藏

Copyright©北京勤云科技发展有限公司  京ICP备09084417号