Overexpression of Bcl-2 attenuates apoptosis and protects against myocardial I/R injury in transgenic mice

1  Cecile Cox Quillen Laboratory of Geriatrics, James H. Quillen School of Medicine, East Tennessee State University and James H. Quillen Veterans Affairs Medical Center, Johnson City, Tennessee 37614; and 2  Institute of Chemical Toxicology, Wayne State University, Detroit, Michigan 48201 To test w...

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Published in:American journal of physiology. Heart and circulatory physiology 2001-05, Vol.280 (5), p.H2313-H2320
Main Authors: Chen, Zhongyi, Chua, Chu Chang, Ho, Ye-Shih, Hamdy, Ronald C, Chua, Balvin H. L
Format: Article
Language:English
Subjects:
Animals
Apoptosis - physiology
Gene Expression - physiology
Humans
In Situ Nick-End Labeling
L-Lactate Dehydrogenase - metabolism
Mice
Mice, Transgenic
Myocardial Reperfusion Injury - pathology
Myocardial Reperfusion Injury - physiopathology
Myocardium - chemistry
Myocardium - enzymology
Myocardium - pathology
Proto-Oncogene Proteins c-bcl-2 - analysis
Proto-Oncogene Proteins c-bcl-2 - genetics
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Summary:1  Cecile Cox Quillen Laboratory of Geriatrics, James H. Quillen School of Medicine, East Tennessee State University and James H. Quillen Veterans Affairs Medical Center, Johnson City, Tennessee 37614; and 2  Institute of Chemical Toxicology, Wayne State University, Detroit, Michigan 48201 To test whether the antiapoptotic protein Bcl-2 prevents apoptosis and injury of cardiomyocytes after ischemia-reperfusion (I/R), we generated a line of transgenic mice that carried a human Bcl-2 transgene under the control of a mouse -myosin heavy chain promoter. High levels of human Bcl-2 transcripts and 26-kDa Bcl-2 protein were expressed in the hearts of transgenic mice. Functional recovery of the transgenic hearts significantly improved when they were perfused as Langendorff preparations. This protection was accompanied by a threefold decrease in lactate dehydrogenase (LDH) released from the transgenic hearts. The transgenic mice were subjected to 50 min of ligation of the left descending anterior coronary artery followed by reperfusion. The infarct sizes, expressed as a percentage of the area at risk, were significantly smaller in the transgenic mice than in the nontransgenic mice (36.6 ±   5 vs 69.9 ± 7.3%, respectively). In hearts subjected to 30 min of coronary artery occlusion followed by 3 h of reperfusion, Bcl-2 transgenic hearts had significantly fewer terminal deoxynucleodidyl-transferase nick-end labeling-positive or in situ oligo ligation-positive myocytes and a less prominent DNA fragmentation pattern. Our results demonstrate that overexpression of Bcl-2 renders the heart more resistant to apoptosis and I/R injury. heart apoptosis; ischemia-reperfusion injury
ISSN:0363-6135
1522-1539
DOI:10.1152/ajpheart.2001.280.5.h2313