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Load effects on gene expression during cardiac hypertrophy

J D Rozich1, M A Barnes, P G Schmid

  • 1Department of Medicine, Gazes Cardiac Research Institute, Medical University of South Carolina, Charleston, USA.

Journal of Molecular and Cellular Cardiology
|January 1, 1995
PubMed
Summary
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Hemodynamic load alone can initiate cardiac hypertrophy by inducing immediate early genes and atrial natriuretic factor (ANF). This study demonstrates that increased right ventricular pressure overload is sufficient to trigger these early molecular events in the heart.

Area of Science:

  • Cardiovascular Physiology
  • Molecular Cardiology
  • Cardiac Remodeling

Background:

  • Hemodynamic load is a key regulator of cardiac mass and a potential trigger for cardiac hypertrophy.
  • Immediate early genes (IEGs) and fetal gene re-expression, such as atrial natriuretic factor (ANF), are markers of this process.
  • Previous models lacked quantification of load and control for confounding systemic factors.

Purpose of the Study:

  • To determine if pressure-induced hemodynamic load alone is sufficient to induce immediate early genes and initiate cardiac hypertrophy.
  • To investigate the role of right ventricular pressure overload in regulating cardiac gene expression.
  • To differentiate the effects of localized load from systemic variables on gene expression.

Main Methods:

Related Experiment Videos

  • Created two models of right ventricular pressure overload in cats via pulmonary artery occlusion (balloon or band).
  • Utilized Northern blot analysis to quantify mRNA levels of c-fos, egr-1, alpha-skeletal actin, and ANF in right and left ventricles.
  • Measured serum catecholamine concentrations and total RNA content to assess systemic effects and hypertrophic growth.

    • Main Results:

    • Right ventricular pressure overload increased RV systolic pressure without altering serum catecholamine levels.
    • RV/LV ratios of egr-1 and c-fos mRNA increased with acute (1-4h) but not chronic (48h) pressure overload.
    • ANF expression was induced in the RV after 48h of pressure overload, and total RNA increased, indicating hypertrophic growth initiation.

    Conclusions:

    • Increased hemodynamic load alone is sufficient to induce immediate early genes and atrial natriuretic factor (ANF) expression.
    • Load-induced changes in IEG and ANF expression precede overt hypertrophic growth.
    • This study provides evidence that pressure overload initiates molecular events leading to cardiac hypertrophy, independent of systemic factors.