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

Item Type:Article
Title:Cardiac gene expression profile in rats with terminal heart failure and cachexia
Creators Name:Wellner, M. and Dechend, R. and Park, J.K. and Shagdasuren, E. and Al-Saadi, N. and Kirsch, T. and Gratze, P. and Schneider, W. and Meiners, S. and Fiebeler, A. and Haller, H. and Luft, F.C. and Mueller, D.N.
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 α/β-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-β, 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.
Keywords:Affymetrix Gene Array, Angiotensin II, Cardiac Damage, Double Transgenic Rats, Hypertrophy, Animals, Rats
Source:Physiological Genomics
Publisher:American Physiological Society
Page Range:256-267
Date:1 January 2005
Official Publication:https://doi.org/10.1152/physiolgenomics.00165.2004
PubMed:View item in PubMed

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