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Cardiac functional improvement by a human Bcl‐2 transgene in a mouse model of ischemia/reperfusion injury
Author(s) -
Brocheriou Valérie,
Hagège Albert A.,
Oubenaïssa Abdou,
Lambert Martine,
Mallet Vincent O.,
Duriez Micheline,
Wassef Michel,
Kahn Axel,
Menasché Philippe,
Gilgenkrantz Hélène
Publication year - 2000
Publication title -
the journal of gene medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.689
H-Index - 91
eISSN - 1521-2254
pISSN - 1099-498X
DOI - 10.1002/1521-2254(200009/10)2:5<326::aid-jgm133>3.0.co;2-1
Subject(s) - tunel assay , transgene , apoptosis , genetically modified mouse , ejection fraction , ischemia , reperfusion injury , cardiology , medicine , cardiac function curve , myocardial infarction , biology , immunohistochemistry , heart failure , biochemistry , gene
Background Apoptosis has been shown to contribute to myocardial reperfusion injury. It has been suggested that, in reducing the apoptotic component within the ischemic area at risk, Bcl‐2 overexpression could lead to a ventricular function improvement. Methods Transgenic mice overexpressing the anti‐apoptotic human Bcl‐2 cDNA in heart were subjected to a 1‐h left coronary artery occlusion followed by a 24‐h reperfusion. At the end of the experiment, left ventricular function was assessed by two‐dimensional echocardiography. After sacrifice, the area at risk (AR) and the infarct area (IA) were determined by Evans blue and triphenyltetrazolium chloride staining, respectively. The extent of apoptosis was assessed by the TUNEL method. Non‐transgenic littermates served as controls. Results Baseline AR was not different between Bcl‐2 transgenic mice and their wild‐type littermates. In contrast, left ventricular ejection fraction was significantly improved in the transgenic mice line (61.25±4.0%) compared to non‐transgenic littermates (43.2±5.0%, p <0.01). This functional amelioration was correlated with a significant reduction of infarct size in transgenic animals (IA/AR 18.51±3.4% vs 50.83±8.4% in non‐transgenic littermates). Finally, apoptotic nuclei were less numerous in transgenic mice than in controls as quantified by TUNEL analysis (8.1±2.2% vs 20.6±4.4%). Conclusions Bcl‐2 overexpression is effective in reducing myocardial reperfusion injury and improving heart function. This benefit correlates with a reduction of cardiomyocyte apoptosis. The apoptotic component of ischemia/reperfusion injury could therefore constitute a new therapeutic target in the acute phase of myocardial infarction. Copyright © 2000 John Wiley & Sons, Ltd.