title: Studies on the role of apoptosis after transient myocardial ischemia: genetic deletion of the executioner caspases-3 and -7 does not limit infarct size and ventricular remodeling.
abstract: Although it is widely accepted that apoptosis may contribute to cell death in myocardial infarction, experimental evidence suggests that adult cardiomyocytes repress the expression of the caspase-dependent apoptotic pathway. The aim of this study was to analyze the contribution of caspase-mediated apoptosis to myocardial ischemia-reperfusion injury. Cardiac-specific caspase-3 deficient/full caspase-7-deficient mice (Casp3/7DKO) and wild type control mice (WT) were subjected to in situ ischemia by left anterior coronary artery ligation for 45 min followed by 24 h or 28 days of reperfusion. Heart function was assessed using M-mode echocardiography. Deletion of caspases did not modify neither infarct size determined by triphenyltetrazolium staining after 24 h of reperfusion (40.0 ± 5.1 % in WT vs. 36.2 ± 3.6 % in Casp3/7DKO), nor the scar area measured by pricosirius red staining after 28 days of reperfusion (41.1 ± 5.4 % in WT vs. 44.6 ± 8.7 % in Casp3/7DKO). Morphometric and echocardiographic studies performed 28 days after the ischemic insult revealed left ventricular dilation and severe cardiac dysfunction without statistically significant differences between WT and Casp3/7DKO groups. These data demonstrate that the executioner caspases-3 and -7 do not significantly contribute to cardiomyocyte death induced by transient coronary occlusion and provide the first evidence obtained in an in vivo model that argues against a relevant role of apoptosis through the canonical caspase pathway in this context.
authors.affiliation: Laboratory of Experimental Cardiology, Department of Cardiology, Vall d'Hebron Research Institute, Universitat Autònoma de Barcelona, Barcelona, Spain.
authors.forename: Javier
authors.initials: J
authors.lastname: Inserte
authors.affiliation: Cell Signalling and Apoptosis group, Departament Ciències Mèdiques Bàsiques, Universitat de Lleida, IRBLleida, Av Rovira Roure, 80, 25198, Lleida, Spain.
authors.forename: Maria
authors.initials: M
authors.lastname: Cardona
authors.affiliation: Laboratory of Experimental Cardiology, Department of Cardiology, Vall d'Hebron Research Institute, Universitat Autònoma de Barcelona, Barcelona, Spain.
authors.forename: Marcos
authors.initials: M
authors.lastname: Poncelas-Nozal
authors.affiliation: Laboratory of Experimental Cardiology, Department of Cardiology, Vall d'Hebron Research Institute, Universitat Autònoma de Barcelona, Barcelona, Spain.
authors.forename: Víctor
authors.initials: V
authors.lastname: Hernando
authors.affiliation: Laboratory of Experimental Cardiology, Department of Cardiology, Vall d'Hebron Research Institute, Universitat Autònoma de Barcelona, Barcelona, Spain.
authors.forename: Úrsula
authors.initials: Ú
authors.lastname: Vilardosa
authors.affiliation: Laboratory of Experimental Cardiology, Department of Cardiology, Vall d'Hebron Research Institute, Universitat Autònoma de Barcelona, Barcelona, Spain.
authors.forename: David
authors.initials: D
authors.lastname: Aluja
authors.affiliation: Facultad de Medicina, Instituto de Ciencias Biomédicas, Universidad de Chile, Santiago, Chile.
authors.forename: Victor M
authors.initials: VM
authors.lastname: Parra
authors.affiliation: Cell Signalling and Apoptosis group, Departament Ciències Mèdiques Bàsiques, Universitat de Lleida, IRBLleida, Av Rovira Roure, 80, 25198, Lleida, Spain. daniel.sanchis@cmb.udl.cat.
authors.forename: Daniel
authors.initials: D
authors.lastname: Sanchis
authors.affiliation: Laboratory of Experimental Cardiology, Department of Cardiology, Vall d'Hebron Research Institute, Universitat Autònoma de Barcelona, Barcelona, Spain. dgdorado@vhebron.net.|Servicio de Cardiologia, Hospital Universitari Vall d'Hebron, Passeig Vall d'Hebron, 119-129, 08035, Barcelona, Spain. dgdorado@vhebron.net.
authors.forename: David
authors.initials: D
authors.lastname: Garcia-Dorado
mesh_terms: D000818:Animals; D017209:Apoptosis; D053148:Caspase 3 / Q000235:genetics / Q000378:metabolism*; D053179:Caspase 7 / Q000235:genetics / Q000378:metabolism*; D005260:Female; D008297:Male; D018345:Mice, Knockout; D009203:Myocardial Infarction / Q000201:enzymology / Q000209:etiology* / Q000473:pathology; D009206:Myocardium / Q000473:pathology; D020257:Ventricular Remodeling
chemical_list: D053148:Caspase 3; D053179:Caspase 7
keywords: Apoptosis; Caspases; Ischemia; Myocardium; Reperfusion