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Selective activation of cardiac angiotensinogen gene expression in post-infarction ventricular remodeling in the rat

Item Type:Article
Title:Selective activation of cardiac angiotensinogen gene expression in post-infarction ventricular remodeling in the rat
Creators Name:Lindpaintner, K., Lu, W., Niedermaier, N., Schieffer, B., Just, H., Ganten, D. and Drexler, H.
Abstract:Recent studies in both experimental animals and man have demonstrated the unique efficacy of converting enzyme inhibitors to prevent or attenuate ventricular remodeling after myocardial infarction. Concomitantly, evidence for a trophic role of the renin-angiotensin system (RAS), as well as for the existence of an intracardiac tissue-resident RAS, has been presented, raising the question whether altered regulation of this cardiac RAS may be associated with the process of ventricular remodeling. We conducted the present study to examine whether cardiac angiotensinogen gene expression is altered after myocardial infarction. Experiments were performed in rats 5 and 25 days after ligation of the left coronary artery or sham operation. Coronary artery ligation resulted in relative infarct sizes averaging 29% and 36% of total left ventricular mass at 5 and 25 days and in marked elevations of left ventricular end-diastolic pressure (LVEDP). Angiotensinogen mRNA levels, measured by solution hybridization assay and confirmed in a second, independent experimental group by RNAse protection assay, were significantly elevated in the non-infarcted portion of the left ventricle at 5 days after infarction when compared to the sham group (22.1 + 3.3 vs. 13.4 +/- 2.0 fg/microgram total RNA; ratio of densitometric absorbance for angiotensinogen/beta-actin: 0.356 +/- 0.041 vs. 0.156 +/- 0.02), and showed a significant correlation with infarct size (r = 0.93). At 25 days, angiotensinogen gene expression had returned to control values. Similarly, no significant differences in angiotensinogen mRNA levels between animals with and without infarction were found in other cardiac tissues (atria, right ventricle). Plasma renin activity was significantly increased over baseline in the infarct group at 5, but not at 25 days. Our results demonstrate that acute hemodynamic embarrassment early after LV infarction is associated with augmented angiotensinogen gene expression. The potential significance of this finding is discussed.
Keywords:Renin Angiotensin System, Heart, Myocardial Infarction, Remodeling, Angiotensinogen, Gene Expression, Animals, Rats
Source:Journal of Molecular and Cellular Cardiology
Page Range:133-143
Date:February 1993
Official Publication:https://doi.org/10.1006/jmcc.1993.1017
PubMed:View item in PubMed

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