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


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.
D000256:Adenoviridae / Q000235:genetics*; D000818:Animals; D017209:Apoptosis; D015153:Blotting, Western; D002908:Chronic Disease; D004452:Echocardiography; D019254:Genes, bcl-2; D015316:Genetic Therapy; D005822:Genetic Vectors; D006333:Heart Failure / Q000209:etiology / Q000517:prevention & control*; D009203:Myocardial Infarction / Q000473:pathology; D015428:Myocardial Reperfusion Injury / Q000150:complications* / Q000000981:diagnostic imaging / Q000473:pathology; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000235:genetics / Q000378:metabolism; D011817:Rabbits; D016277:Ventricular Function, Left; D020257:Ventricular Remodeling
D019253:Proto-Oncogene Proteins c-bcl-2