title: Entrance in mitosis of adult cardiomyocytes in ischemic pig hearts after plasmid-mediated rhVEGF165 gene transfer.
abstract: Replacement of the cell loss occurring after acute myocardial infarction has been proposed as a potential treatment to prevent heart remodeling and failure. On account that cardiomyocytes express VEGF receptors and that VEGF triggers mitogen-activated protein kinases, we investigated if VEGF gene transfer may induce cardiomyocyte replication. In a pig model of chronic myocardial ischemia achieved by Ameroid occlusion of the left circumflex coronary artery, we observed that direct intramyocardial injection of a plasmid encoding human VEGF(165) induced a several-fold increase in cardiomyocyte mitotic index and in the number of cardiomyocyte nuclei per unit volume as compared with pigs receiving plasmid devoid of gene. Despite images of conventional cytokinesis were not observed, the fact that caryokinesis is an obligatory step for cell division suggests that our finding may contribute to the issue of heart regeneration and may potentially widen the therapeutic spectrum of VEGF gene transfer.
authors.affiliation: Department of Pathology, Favaloro University, Buenos Aires, Argentina.
authors.forename: R
authors.initials: R
authors.lastname: Laguens
authors.forename: P
authors.initials: P
authors.lastname: Cabeza Meckert
authors.forename: G
authors.initials: G
authors.lastname: Vera  Janavel
authors.forename: H
authors.initials: H
authors.lastname: Del Valle
authors.forename: E
authors.initials: E
authors.lastname: Lascano
authors.forename: J
authors.initials: J
authors.lastname: Negroni
authors.forename: P
authors.initials: P
authors.lastname: Werba
authors.forename: L
authors.initials: L
authors.lastname: Cuniberti
authors.forename: V
authors.initials: V
authors.lastname: Martínez
authors.forename: C
authors.initials: C
authors.lastname: Melo
authors.forename: M
authors.initials: M
authors.lastname: Papouchado
authors.forename: R
authors.initials: R
authors.lastname: Ojeda
authors.forename: M
authors.initials: M
authors.lastname: Criscuolo
authors.forename: A
authors.initials: A
authors.lastname: Crottogini
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D016228:Endothelial Growth Factors / Q000032:analysis / Q000235:genetics*; D015316:Genetic Therapy / Q000379:methods*; D005822:Genetic Vectors / Q000008:administration & dosage*; D007150:Immunohistochemistry; D036341:Intercellular Signaling Peptides and Proteins / Q000032:analysis / Q000235:genetics*; D008222:Lymphokines / Q000032:analysis / Q000235:genetics*; D008856:Microscopy, Fluorescence; D008938:Mitosis; D023421:Models, Animal; D017202:Myocardial Ischemia / Q000628:therapy*; D032383:Myocytes, Cardiac / Q000378:metabolism / Q000473:pathology*; D011897:Random Allocation; D020133:Reverse Transcriptase Polymerase Chain Reaction; D034421:Sus scrofa; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors
chemical_list: D016228:Endothelial Growth Factors; D036341:Intercellular Signaling Peptides and Proteins; D008222:Lymphokines; C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors