eprintid: 1311106
rev_number: 37
eprint_status: archive
userid: 608
dir: disk0/01/31/11/06
datestamp: 2011-06-19 20:50:53
lastmod: 2021-11-07 00:40:08
status_changed: 2013-11-14 11:59:48
type: article
metadata_visibility: show
item_issues_count: 0
creators_name: Waghabi, MC
creators_name: Coutinho-Silva, R
creators_name: Feige, JJ
creators_name: Higuchi, MD
creators_name: Becker, D
creators_name: Burnstock, G
creators_name: de Araujo-Jorge, TC
title: Gap junction reduction in cardiomyocytes following transforming growth factor- beta treatment and Trypanosoma cruzi infection
ispublished: pub
divisions: UCL
divisions: B02
divisions: C08
divisions: D09
keywords: gap junction, heart, Chagas disease, transforming growth factor-beta, connexin 43, PARASITE CYCLE COMPLETION, CHAGAS HEART-DISEASE, INTERCELLULAR COMMUNICATION, VENTRICULAR MYOCARDIUM, CONNEXIN43 EXPRESSION, DOWN-REGULATION, MESSENGER-RNA, P2 RECEPTORS, TGF-BETA, IN-VITRO
note: All the contents of Memórias do Instituto Oswaldo Cruz journal, except where otherwise noted, is licensed under a Creative Commons Attribution License (CC-BY).
abstract: Gap junction connexin-43 (Cx43) molecules are responsible for electrical impulse conduction in the heart and are affected by transforming growth factor-beta (TGF-beta). This cytokine increases during Trypanosoma cruzi infection, modulating fibrosis and the parasite cell cycle. We studied Cx43 expression in cardiomyocytes exposed or not to TGF-beta T. cruzi, or SB-431542, an inhibitor of TGF-beta receptor type I (ALK-5). Cx43 expression was also examined in hearts with dilated cardiopathy from chronic Chagas disease patients, in which TGF-beta signalling had been shown previously to be highly activated. We demonstrated that TGF-beta treatment induced disorganised gap junctions in non-infected cardiomyocytes, leading to a punctate, diffuse and non-uniform Cx43 staining. A similar pattern was detected in T. cruzi-infected cardiomyocytes concomitant with high TGF-beta secretion. Both results were reversed if the cells were incubated with SB-431542. Similar tests were performed using human chronic chagasic patients and we confirmed a down-regulation of Cx43 expression, an altered distribution of plaques in the heart and a significant reduction in the number and length of Cx43 plaques, which correlated negatively with cardiomegaly. We conclude that elevated TGF-beta levels during T. cruzi infection promote heart fibrosis and disorganise gap junctions, possibly contributing to abnormal impulse conduction and arrhythmia that characterise severe cardiopathy in Chagas disease.
date: 2009-12
publisher: FUNDACO OSWALDO CRUZ
official_url: http://www.scielo.br/scielo.php?pid=0074-0276&script=sci_serial
vfaculties: VFLS
oa_status: green
full_text_type: pub
language: eng
primo: open
primo_central: open_green
article_type_text: Article
verified: verified_batch
elements_source: Web of Science
elements_id: 318565
language_elements: EN
lyricists_name: Becker, David
lyricists_name: Burnstock, Geoffrey
lyricists_id: DLBEC91
lyricists_id: GBURN46
full_text_status: public
publication: Memórias do Instituto Oswaldo Cruz
volume: 104
number: 8
pagerange: 1083-1090
issn: 0074-0276
citation:        Waghabi, MC;    Coutinho-Silva, R;    Feige, JJ;    Higuchi, MD;    Becker, D;    Burnstock, G;    de Araujo-Jorge, TC;      (2009)    Gap junction reduction in cardiomyocytes following transforming growth factor- beta treatment and Trypanosoma cruzi infection.                   Memórias do Instituto Oswaldo Cruz , 104  (8)   pp. 1083-1090.          Green open access   
 
document_url: https://discovery.ucl.ac.uk/id/eprint/1311106/1/04.pdf