Cardiac gene expression profile in rats with terminal heart failure and cachexia

• Published in: Physiological genomics 2005-02, Vol.20 (3), p.256-267
• Main Authors: Wellner, Maren, Dechend, Ralf, Park, Joon-Keun, Shagdarsuren, Erdenechimeg, Al-Saadi, Nidal, Kirsch, Torsten, Gratze, Petra, Schneider, Wolfgang, Meiners, Silke, Fiebeler, Anette, Haller, Hermann, Luft, Friedrich C, Muller, Dominik N
• Format: Article
• Language: English
• Subjects: Animals; Cachexia - complications; Cachexia - genetics; Databases, Nucleic Acid; Disease Models, Animal; Echocardiography; Gene Expression Profiling; Heart - physiopathology; Heart Failure - complications; Heart Failure - diagnostic imaging; Heart Failure - genetics; Male; Rats; Rats, Sprague-Dawley
• ISSN: 1094-8341; 1531-2267
• DOI: 10.1152/physiolgenomics.00165.2004

1 HELIOS Klinikum-Berlin, Franz Volhard Clinic, and Medical Faculty of the Charité, Humboldt University of Berlin 2 Max-Delbrück-Center for Molecular Medicine, Berlin-Buch 3 Department of Medicine-Nephrology, Hannover Medical School, Hannover 4 Department of Cardiology, Charité Campus Mitte, Berlin, Germany 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 /ß-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-ß, 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. double transgenic rats; angiotensin II; cardiac damage; hypertrophy; Affymetrix gene array