Cardiac gene expression profile in rats with terminal heart failure and cachexia.
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.
Wellner
Maren
M
HELIOS Klinikum-Berlin, Franz Volhard Clinic, and Medical Faculty of the Charité, Humboldt University of Berlin, Germany.
Dechend
Ralf
R
Park
Joon-Keun
JK
Shagdarsuren
Erdenechimeg
E
Al-Saadi
Nidal
N
Kirsch
Torsten
T
Gratze
Petra
P
Schneider
Wolfgang
W
Meiners
Silke
S
Fiebeler
Anette
A
Haller
Hermann
H
Luft
Friedrich C
FC
Muller
Dominik N
DN
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