gms | German Medical Science

27. Wissenschaftlicher Kongress der Deutschen Hochdruckliga

Deutsche Liga zur Bekämpfung des hohen Blutdrucks – Deutsche Hypertonie Gesellschaft e. V.

26. bis 29.11.2003, Bonn

Altered gene expression proflie in rats with and without terminal heart failure

Unterschiedliche Genexpression im Herzen von Ratten mit und ohne terminaler Herzinsuffizienz

Meeting Abstract (Hypertonie 2003)

  • R. Dechend
  • N. Al-Saadi
  • T. Kirsch
  • presenting/speaker M. Wellner
  • A. Fiebeler
  • H. Haller
  • F.C. Luft
  • D.N. Müller

Hypertonie 2003. 27. Wissenschaftlicher Kongress der Deutschen Hochdruckliga. Bonn, 26.-29.11.2003. Düsseldorf, Köln: German Medical Science; 2004. Doc03hochP35

Die elektronische Version dieses Artikels ist vollständig und ist verfügbar unter: http://www.egms.de/de/meetings/hoch2003/03hoch135.shtml

Veröffentlicht: 11. November 2004

© 2004 Dechend et al.
Dieser Artikel ist ein Open Access-Artikel und steht unter den Creative Commons Lizenzbedingungen (http://creativecommons.org/licenses/by-nc-nd/3.0/deed.de). Er darf vervielf&aauml;ltigt, verbreitet und &oauml;ffentlich zug&aauml;nglich gemacht werden, vorausgesetzt dass Autor und Quelle genannt werden.


Gliederung

Text

Seven to 8-week old double transgenic rats (dTGR) overexpressing the human renin and angiotensinogen genes die of terminal heart failure (THF) and cachexia. To elucidate the mechanisms of angiotensin (Ang) II-induced cardiac injury, we analyzed gene expression patterns in THF-dTGR and compared these rats with preterminal dTGR, losartan-treated (LOS)-dTGR and non-transgenic rats (SD). Body weight of THF-dTGR was significantly lower than all other groups. At sacrifice, THF-dTGR had blood pressures of 228±7 mm Hg; cardiac hypertophy index 6.2±0.1 mg/g; echocardiography E<A; and albuminuria 21±3 mg/d. Preterminal dTGR had blood pressures of 197±5 mm Hg; cardiac hypertrophy index 5.1±0.1 mg/g; E<A; and albuminuria 17±3 mg/d. LOS-dTGR had blood pressures of 141±6 mm Hg; cardiac hypertrophy index 3.7±0.1 mg/g; E>A; and albuminuria 1±0.2 mg/d. For SD blood pressure was 112±4 mm Hg; cardiac hypertrophy index 3.6±0.1 mg/g; E>A; and albuminuria 0.2±0.02 mg/d. Total RNA of left ventricular heart tissue was isolated and the Affymetrix system was used. THF-dTGR (vs. other groups) showed an upregulation of various genes (altered >factor 2), which could be grouped into transcription factors (CEBP-beta, c-fos), coagulation (PAI-1), remodeling components (TIMP-1, lysyl oxidase), eicosanoid synthesis (lipoxygenase, cyclooxygenase), signal transduction (Rab-2, adenylate cyclase activating polypeptide-1), heat shock proteins (HSP70, HSP27, Heme oxygenase), apoptosis (bax, bcl-2, ass X protein), oxidized low density lipoprotein receptor 1, CYP family (CYP3a2, CYP3a18, CYP2b15, CYP2c23, CYP7a1, CYP2c7) and ESTs. Several hypertrophy markers were elevated in rats preterminal dTGR compared to LOS-dTGR and SD. LOS-dTGR and SD had similar expression profiles. These data show that THF-dTGR show an altered expression profile compared to preterminal dTGR. AT1 receptor blockade reverts the expression profiles to normal.