title: Cardiac gene expression profile in rats with terminal heart failure and cachexia.
abstract: About one-half of double transgenic rats (dTGR) overexpressing the human renin and angiotensinogen genes die by age 7 wk of terminal heart failure (THF); the other (preterminal) one-half develop cardiac damage but survive. Our study's aim was to elucidate cardiac gene expression differences in dTGR-THF compared with dTGR showing compensated cardiac hypertrophy but not yet THF. dTGR treated with losartan (LOS) and nontransgenic rats (SD) served as controls. THF-dTGR body weight was significantly lower than for all other groups. At death, THF-dTGR had blood pressures of 228 +/- 7 mmHg (cardiac hypertrophy index 6.2 +/- 0.1 mg/g). Tissue Doppler showed reduced peak early (Ea) to late (Aa) diastolic expansion in THF-dTGR, indicating diastolic function. Preterminal dTGR had blood pressures of 197 +/- 5 mmHg (cardiac hypertrophy index 5.1 +/- 0.1 mg/g); Ea < Aa compared with LOS-dTGR (141 +/- 6 mmHg; 3.7+/-0.1 mg/g; Ea > Aa) and SD (112 +/- 4 mmHg; 3.6 +/- 0.1 mg/g; Ea > Aa). Left ventricular RNA was isolated for the Affymetrix system and TaqMan RT-PCR. THF-dTGR and dTGR showed upregulation of hypertrophy markers and alpha/beta-myosin heavy chain switch to the fetal isoform. THF-dTGR (vs. dTGR) showed upregulation of 239 and downregulation of 150 genes. Various genes of mitochodrial respiratory chain and lipid catabolism were reduced. In addition, genes encoding transcription factors (CEBP-beta, c-fos, Fra-1), coagulation, remodeling/repair components (HSP70, HSP27, heme oxygenase), immune system (complement components, IL-6), and metabolic pathway were differentially expressed. In contrast, LOS-dTGR and SD had similar expression profiles. These data demonstrate that THF-dTGR show an altered expression profile compared with preterminal dTGR.
authors.affiliation: HELIOS Klinikum-Berlin, Franz Volhard Clinic, and Medical Faculty of the Charité, Humboldt University of Berlin, Germany.
authors.forename: Maren
authors.initials: M
authors.lastname: Wellner
authors.forename: Ralf
authors.initials: R
authors.lastname: Dechend
authors.forename: Joon-Keun
authors.initials: JK
authors.lastname: Park
authors.forename: Erdenechimeg
authors.initials: E
authors.lastname: Shagdarsuren
authors.forename: Nidal
authors.initials: N
authors.lastname: Al-Saadi
authors.forename: Torsten
authors.initials: T
authors.lastname: Kirsch
authors.forename: Petra
authors.initials: P
authors.lastname: Gratze
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Schneider
authors.forename: Silke
authors.initials: S
authors.lastname: Meiners
authors.forename: Anette
authors.initials: A
authors.lastname: Fiebeler
authors.forename: Hermann
authors.initials: H
authors.lastname: Haller
authors.forename: Friedrich C
authors.initials: FC
authors.lastname: Luft
authors.forename: Dominik N
authors.initials: DN
authors.lastname: Muller
mesh_terms: D000818:Animals; D002100:Cachexia / Q000150:complications / Q000235:genetics*; D030561:Databases, Nucleic Acid; D004195:Disease Models, Animal; D004452:Echocardiography; D020869:Gene Expression Profiling; D006321:Heart / Q000503:physiopathology*; D006333:Heart Failure / Q000150:complications / Q000000981:diagnostic imaging / Q000235:genetics*; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley