Stretching cardiac myocytes stimulates protooncogene expression.

Area of Science:

• Cardiovascular Biology
• Molecular Cardiology
• Cellular Mechanotransduction

Background:

• Cardiac hypertrophy involves early induction of cellular protooncogenes.
• Pressure overload is a known trigger for these molecular changes.
• The direct role of mechanical stimuli in cardiac gene expression remained unclear.

Purpose of the Study:

• To investigate if mechanical forces directly induce specific gene expression in cardiomyocytes.
• To elucidate the relationship between cellular stretching and protooncogene activation in the heart.

Main Methods:

• Cultured neonatal rat cardiocytes subjected to mechanical stretching in elastic silicone dishes.
• Quantified c-fos protooncogene expression and mRNA levels post-stretching.
• Utilized cycloheximide to assess protein synthesis involvement.
• Employed reporter gene assays (chloramphenicol acetyltransferase) linked to the fos gene promoter.

Main Results:

• Myocyte stretching dose-dependently stimulated c-fos protooncogene expression.
• c-fos mRNA levels rapidly increased within 15 minutes, peaking at 30 minutes.
• Stretching enhanced amino acid incorporation into proteins.
• Reporter gene activation confirmed transcriptional regulation by mechanical stimuli.
• Cycloheximide treatment potentiated the stretching-induced increase in c-fos mRNA.

Conclusions:

• Mechanical loading directly regulates gene transcription in cardiomyocytes.
• The c-fos protooncogene is an early-response gene to mechanical stress in cardiac cells.
• Humoral factors are not required for mechanical stimuli-induced gene regulation in this context.