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Surgically Induced Cardiac Volume Overload by Aortic Regurgitation in Mouse
08:12

Surgically Induced Cardiac Volume Overload by Aortic Regurgitation in Mouse

Published on: August 30, 2022

Gender differences in apoptotic signaling in heart failure due to volume overload

Melissa R Dent1, Paramjit S Tappia, Naranjan S Dhalla

  • 1Department of Physiology, Institute of Cardiovascular Sciences, St. Boniface General Hospital Research Centre, Winnipeg, MB, Canada.

Apoptosis : an International Journal on Programmed Cell Death
|December 31, 2009
PubMed

Insights

Sex differences emerge in heart failure due to volume overload. Male rats show increased apoptosis, while females exhibit resistance, linked to specific protein regulation and estrogen effects.

Area of Science:

  • Cardiovascular Biology
  • Cellular and Molecular Medicine
  • Physiology

Background:

  • Cardiac hypertrophy and heart failure are significant cardiovascular conditions.
  • Sex-based differences in disease progression and molecular mechanisms are increasingly recognized.
  • Volume overload is a common cause of cardiac remodeling and failure.

Purpose of the Study:

  • To investigate sex-specific regulation of apoptosis-related proteins in cardiac hypertrophy and heart failure.
  • To elucidate the role of BAX, caspases, and Bcl-2 family proteins in male and female rat hearts under volume overload.
  • To determine the influence of estrogen on cardiomyocyte apoptosis and resistance.

Main Methods:

  • Induction of cardiac volume overload using an arteriovenous (AV) shunt in male and female rats.
  • Hemodynamic assessment and cardiac characterization at 4 and 16 weeks post-AV shunt.
  • Western blot analysis to quantify pro- and anti-apoptotic protein expression (BAX, caspases 3 & 9, phospho-Bad, phospho-Bcl-2).
  • Ovariectomy and 17-beta estradiol treatment in female rats to assess hormonal effects.

Main Results:

  • Cardiac hypertrophy was observed in both sexes at 4 weeks; heart failure developed only in males at 16 weeks.
  • Apoptosis increased in male hearts but decreased in female hearts at 16 weeks.
  • Males exhibited increased pro-apoptotic proteins (BAX, caspases) and decreased phospho-Bcl-2.
  • Females showed increased phospho-Bcl-2; ovariectomy abolished this, while estradiol restored it.

Conclusions:

  • Downregulation of phospho-Bcl-2 and upregulation of BAX contribute to cardiomyocyte apoptosis in male heart failure due to volume overload.
  • Upregulation of phospho-Bcl-2, mediated by estrogen, confers resistance to cardiomyocyte apoptosis in female hearts.
  • Estrogen plays a protective role against apoptosis in the female heart during volume overload-induced heart failure.

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