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Alterations in both death and survival signals for apoptosis in heart failure due to volume overload

Melissa R Dent1, Samarjit Das, Naranjan S Dhalla

  • 1Institute of Cardiovascular Sciences, St. Boniface Hospital Research Centre, 351 Tache Avenue, Winnipeg, Manitoba, Canada.

Journal of Molecular and Cellular Cardiology
|October 13, 2007
PubMed

Insights

Volume overload heart failure increases cardiomyocyte apoptosis via the Akt survival pathway. This study found reduced Bcl-2 and increased BAX, suggesting a role in heart remodeling.

Area of Science:

  • Cardiology
  • Molecular Biology
  • Pathophysiology

Background:

  • Heart failure is linked to cardiomyocyte apoptosis, but mechanisms in volume overload are unclear.
  • Understanding these mechanisms is crucial for treating heart failure.

Purpose of the Study:

  • To investigate signaling pathways regulating apoptosis in volume overload-induced heart failure.
  • To examine the roles of Akt, Bcl-2, and BAX in cardiomyocyte apoptosis.

Main Methods:

  • Volume overload heart failure was induced in rats using an arteriovenous (AV) shunt.
  • Cardiac function was assessed hemodynamically and via echocardiography.
  • Western blot analysis was used to study protein levels in the left ventricle.

Main Results:

  • AV shunt rats developed severe heart failure with elevated tumor necrosis factor-alpha and apoptosis.
  • Increased BAX and caspase 3/9 proteins were observed in failing hearts.
  • Decreased phosphorylated Akt and Bcl-2 levels indicated Akt-dependent survival pathway downregulation.

Conclusions:

  • Volume overload heart failure involves cardiomyocyte apoptosis.
  • Downregulation of the Akt/Bcl-2 survival pathway and upregulation of BAX contribute to apoptosis.
  • These molecular alterations are implicated in the pathogenesis of heart failure.

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