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

Circulation. 2002 Sep 24;106(12 Suppl 1):I212-7.


Background: Apoptosis secondary to acute ischemia and chronic remodeling is implicated as a mediator of heart failure. This study was designed to assess the effect of in vivo viral gene transfer of the anti-apoptotic factor Bcl-2 to block apoptosis and preserve ventricular geometry and function.

Methods and results: In a rabbit model of regional ischemia followed by reperfusion, an experimental group treated with adeno-Bcl-2 was compared with a control group receiving empty vector adeno-null. Function was assessed by echocardiography, and sonomicrometry of the border zone was compared with the normal left ventricle (LV). Animals were killed at 6 weeks, and an additional group was killed after 3 days to see whether virus administration conferred an immediate effect. Animals that were administered Bcl-2 maintained higher ejection fractions at 2, 4, and 6 weeks compared with controls. Sonomicrocrystals demonstrated greater protection of border zone fractional shortening at 6 weeks. The Bcl-2 group had superior preservation of LV geometry with less ventricular dilatation and wall thinning. There was also reduced apoptosis compared with the controls. Finally, in the animals killed at 3 days, no functional difference was observed between the Bcl-2 and control groups.

Conclusions: Gene transfer of Bcl-2 preserves LV function after ischemia despite the absence of an observed acute protective effect. The benefit at 6 weeks is postulated to result from a Bcl-2-mediated reduction in apoptosis and ventricular remodeling. Adeno-Bcl-2 administration offers a potential strategy to protect the heart from late postischemic heart failure.

Publication types

  • Comparative Study
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adenoviridae / genetics*
  • Animals
  • Apoptosis*
  • Blotting, Western
  • Chronic Disease
  • Echocardiography
  • Genes, bcl-2*
  • Genetic Therapy*
  • Genetic Vectors
  • Heart Failure / etiology
  • Heart Failure / prevention & control*
  • Myocardial Infarction / pathology
  • Myocardial Reperfusion Injury / complications*
  • Myocardial Reperfusion Injury / diagnostic imaging
  • Myocardial Reperfusion Injury / pathology
  • Proto-Oncogene Proteins c-bcl-2 / genetics
  • Proto-Oncogene Proteins c-bcl-2 / metabolism
  • Rabbits
  • Ventricular Function, Left
  • Ventricular Remodeling


  • Proto-Oncogene Proteins c-bcl-2