Viral gene transfer of the antiapoptotic factor Bcl-2 protects against chronic postischemic heart failure

Subhasis Chatterjee1, Allan S Stewart, Lawrence T Bish

  • 1Division of Cardiothoracic Surgery, University of Pennsylvania School of Medicine, Philadelphia, Pa 19104, USA.

Circulation
|October 2, 2002
PubMed
Abstract

Insights

Gene transfer of Bcl-2 effectively preserves heart function and structure after ischemia by reducing apoptosis and remodeling, offering a potential therapy for postischemic heart failure.

Area of Science:

  • Cardiovascular Research
  • Gene Therapy
  • Molecular Cardiology

Background:

  • Apoptosis contributes to heart failure following ischemia and chronic remodeling.
  • Viral gene transfer of Bcl-2 aims to block apoptosis and preserve cardiac function.

Purpose of the Study:

  • To evaluate the efficacy of in vivo adeno-Bcl-2 gene transfer in preventing apoptosis and preserving ventricular geometry and function after ischemia.
  • To assess the long-term effects of Bcl-2 gene transfer on cardiac remodeling and heart failure progression.

Main Methods:

  • A rabbit model of regional ischemia-reperfusion was used.
  • Experimental group received adeno-Bcl-2; control group received adeno-null.
  • Cardiac function assessed by echocardiography and sonomicrometry; apoptosis and ventricular remodeling evaluated at 6 weeks.

Main Results:

  • Bcl-2 treated rabbits maintained higher ejection fractions and superior border zone fractional shortening at 2, 4, and 6 weeks post-ischemia.
  • Significant preservation of left ventricular (LV) geometry, with reduced dilatation and wall thinning observed in the Bcl-2 group.
  • Reduced apoptosis and ventricular remodeling were noted in the Bcl-2 group compared to controls, with no acute functional difference at 3 days.

Conclusions:

  • In vivo gene transfer of Bcl-2 preserves LV function and geometry after ischemia, indicating a potential therapeutic strategy against late postischemic heart failure.
  • The observed benefits at 6 weeks are attributed to Bcl-2-mediated reduction in apoptosis and subsequent ventricular remodeling.
  • Adeno-Bcl-2 administration presents a promising approach to mitigate heart failure progression post-ischemia.

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