title: Cyclin and caveolin expression in an acute model of murine Chagasic myocarditis.
abstract: Chagas' disease caused by the parasite, Trypanosoma cruzi, is accompanied by an acute myocarditis which can be fatal. Mice (A/J strain) infected with T. cruzi (Tulahuen strain) develop an acute myocarditis associated with high parasitemia and uniform mortality. Examination of the myocardium demonstrated myonecrosis, vasculitis and parasite pseudocysts. Immunoblot analysis and quantitative real time PCR of heart lysates demonstrated an increased expression of cell cycle regulatory proteins such as cyclins B1, D1, A1 and E1 and an increased expression of cdk2 when compared with uninfected controls. Extracellular signal-regulated kinase (ERK) was activated. Proliferating cell nuclear antigen (PCNA), endothelin-1, endothelin receptor type A (ET(A)) and endothelin receptor type B (ET(B)) expression were increased. Caveolin-1 is important in the regulation of ERK and cyclin D1. The expression of caveolin-1 as well as caveolin-2 and caveolin-3 was reduced. These data suggest that acute fatal T. cruzi myocarditis is accompanied by changes in cell cycle proteins such as the cyclins and caveolin and that the upregulation of the endothelin pathway may be important in the myocardial abnormalities and mortality observed in this mouse model.
authors.affiliation: Department of Pathology, Albert Einstein College of Medicine, Bronx, New York 10461, USA.
authors.forename: Fnu
authors.initials: F
authors.lastname: Nagajyothi
authors.forename: Mahalia
authors.initials: M
authors.lastname: Desruisseaux
authors.forename: Boumediene
authors.initials: B
authors.lastname: Bouzahzah
authors.forename: Louis M
authors.initials: LM
authors.lastname: Weiss
authors.forename: Daniele dos Santos
authors.initials: Ddos S
authors.lastname: Andrade
authors.forename: Stephen M
authors.initials: SM
authors.lastname: Factor
authors.forename: Philipp E
authors.initials: PE
authors.lastname: Scherer
authors.forename: Chris
authors.initials: C
authors.lastname: Albanese
authors.forename: Michael P
authors.initials: MP
authors.lastname: Lisanti
authors.forename: Herbert B
authors.initials: HB
authors.lastname: Tanowitz
mesh_terms: D000208:Acute Disease; D000818:Animals; D051242:Caveolin 1 / Q000378:metabolism*; D014355:Chagas Disease / Q000150:complications* / Q000378:metabolism; D016213:Cyclins / Q000235:genetics / Q000378:metabolism*; D004195:Disease Models, Animal; D019332:Endothelin-1 / Q000378:metabolism; D005786:Gene Expression Regulation; D008297:Male; D051379:Mice; D009205:Myocarditis / Q000235:genetics / Q000378:metabolism* / Q000469:parasitology / Q000473:pathology*; D012333:RNA, Messenger / Q000235:genetics; D014349:Trypanosoma cruzi / Q000502:physiology
chemical_list: D051242:Caveolin 1; D016213:Cyclins; D019332:Endothelin-1; D012333:RNA, Messenger