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Viral gene transfer of the antiapoptotic factor Bcl-2 protects against chronic postischemic heart failure.
- Source :
-
Circulation [Circulation] 2002 Sep 24; Vol. 106 (12 Suppl 1), pp. I212-7. - Publication Year :
- 2002
-
Abstract
- 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.<br />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.<br />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.
- Subjects :
- Animals
Blotting, Western
Chronic Disease
Echocardiography
Genetic Vectors
Heart Failure etiology
Myocardial Infarction pathology
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
Adenoviridae genetics
Apoptosis
Genes, bcl-2
Genetic Therapy
Heart Failure prevention & control
Myocardial Reperfusion Injury complications
Subjects
Details
- Language :
- English
- ISSN :
- 1524-4539
- Volume :
- 106
- Issue :
- 12 Suppl 1
- Database :
- MEDLINE
- Journal :
- Circulation
- Publication Type :
- Academic Journal
- Accession number :
- 12354736