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Correlation between function and proto-oncogene expression in isolated working rat hearts under various overload
A Horban1, C Kolbeck-Rühmkorff, H G Zimmer
1Department of Physiology, University of Munich, Germany.
Journal of Molecular and Cellular Cardiology
|February 28, 1998
Summary
Norepinephrine and cardiac overload studies in rat hearts show that combined stimuli cause earlier and more prolonged expression of proto-oncogenes c-fos and c-myc, leading to functional decline.
Area of Science:
- Cardiology
- Molecular Biology
- Physiology
Background:
- Cardiac hypertrophy is a significant risk factor for heart failure.
- Proto-oncogenes like c-fos and c-myc play crucial roles in cellular growth and differentiation.
- Understanding the molecular mechanisms underlying cardiac adaptation to stress is vital for developing therapeutic strategies.
Purpose of the Study:
- To investigate the effects of norepinephrine (NE) and pressure/volume overload, alone and in combination, on rat heart function.
- To examine the expression patterns of proto-oncogenes c-fos and c-myc under these conditions.
- To correlate changes in proto-oncogene expression with functional alterations in the working rat heart.
Main Methods:
- Isolated perfused working rat heart model.
- Application of norepinephrine, pressure overload (increased afterload), and volume overload (increased preload).
- Measurement of cardiac function (aortic flow, coronary flow, cardiac output).
- Quantification of c-fos and c-myc mRNA levels using Northern blots and densitometry.
Main Results:
- Norepinephrine increased cardiac output and flow; pressure overload decreased aortic flow; volume overload increased aortic flow and cardiac output.
- Both c-fos and c-myc mRNA levels increased following stimuli, with c-fos showing an earlier and more transient response than c-myc.
- Combined stimuli resulted in earlier and more sustained increases in c-fos and c-myc expression compared to single stimuli.
- Functional parameters deteriorated more significantly under combined stress conditions.
Conclusions:
- Stimuli inducing cardiac hypertrophy in vivo trigger transient and sequential proto-oncogene expression in the isolated working rat heart.
- Combined hypertrophic stimuli elicit a more pronounced and prolonged proto-oncogene response.
- The observed changes in proto-oncogene expression correlate with functional deterioration, highlighting their role in cardiac adaptation and maladaptation.