Entrance in mitosis of adult cardiomyocytes in ischemic pig hearts after plasmid-mediated rhVEGF165 gene transfer
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 tr...
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| Veröffentlicht in: | Gene therapy 2002-12, Vol.9 (24), p.1676-1681 |
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| creator | LAGUENS, R CABEZA MECKERT, P PAPOUCHADO, M OJEDA, R CRISCUOLO, M CROTTOGINI, A VERA JANAVEL, G DEL VALLE, H LASCANO, E NEGRONI, J WERBA, P CUNIBERTI, L MARTINEZ, V MELO, C |
| description | 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. |
| doi_str_mv | 10.1038/sj.gt.3301844 |
| format | Article |
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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.</description><identifier>ISSN: 0969-7128</identifier><identifier>EISSN: 1476-5462</identifier><identifier>DOI: 10.1038/sj.gt.3301844</identifier><identifier>PMID: 12457281</identifier><language>eng</language><publisher>Basingstoke: Nature Publishing Group</publisher><subject>Anesthesia. Intensive care medicine. Transfusions. Cell therapy and gene therapy ; Animals ; Applied cell therapy and gene therapy ; Biological and medical sciences ; Biotechnology ; Cardiomyocytes ; Cell division ; Cells, Cultured ; Coronary artery ; Cytokinesis ; Endothelial Growth Factors - analysis ; Endothelial Growth Factors - genetics ; Fundamental and applied biological sciences. Psychology ; Gene therapy ; Gene transfer ; Genetic Therapy - methods ; Genetic Vectors - administration & dosage ; Health. Pharmaceutical industry ; Heart ; Heart diseases ; Immunohistochemistry ; Industrial applications and implications. Economical aspects ; Intercellular Signaling Peptides and Proteins - analysis ; Intercellular Signaling Peptides and Proteins - genetics ; Ischemia ; Kinases ; Lymphokines - analysis ; Lymphokines - genetics ; Medical sciences ; Microscopy, Fluorescence ; Mitosis ; Models, Animal ; Myocardial infarction ; Myocardial ischemia ; Myocardial Ischemia - therapy ; Myocytes, Cardiac - metabolism ; Myocytes, Cardiac - pathology ; Occlusion ; Protein kinase ; Random Allocation ; Reverse Transcriptase Polymerase Chain Reaction ; Sus scrofa ; Transfusions. Complications. Transfusion reactions. Cell and gene therapy ; Vascular endothelial growth factor ; Vascular Endothelial Growth Factor A ; Vascular Endothelial Growth Factors</subject><ispartof>Gene therapy, 2002-12, Vol.9 (24), p.1676-1681</ispartof><rights>2003 INIST-CNRS</rights><rights>Copyright Nature Publishing Group Dec 2002</rights><rights>Macmillan Publishers Limited 2002.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c2604-34e427640d747a2056e8f59467139ccf13bced2c36a833b6c06c4600c9c099c03</citedby><cites>FETCH-LOGICAL-c2604-34e427640d747a2056e8f59467139ccf13bced2c36a833b6c06c4600c9c099c03</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,776,780,27901,27902</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=14422912$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/12457281$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>LAGUENS, R</creatorcontrib><creatorcontrib>CABEZA MECKERT, P</creatorcontrib><creatorcontrib>PAPOUCHADO, M</creatorcontrib><creatorcontrib>OJEDA, R</creatorcontrib><creatorcontrib>CRISCUOLO, M</creatorcontrib><creatorcontrib>CROTTOGINI, A</creatorcontrib><creatorcontrib>VERA JANAVEL, G</creatorcontrib><creatorcontrib>DEL VALLE, H</creatorcontrib><creatorcontrib>LASCANO, E</creatorcontrib><creatorcontrib>NEGRONI, J</creatorcontrib><creatorcontrib>WERBA, P</creatorcontrib><creatorcontrib>CUNIBERTI, L</creatorcontrib><creatorcontrib>MARTINEZ, V</creatorcontrib><creatorcontrib>MELO, C</creatorcontrib><title>Entrance in mitosis of adult cardiomyocytes in ischemic pig hearts after plasmid-mediated rhVEGF165 gene transfer</title><title>Gene therapy</title><addtitle>Gene Ther</addtitle><description>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.</description><subject>Anesthesia. Intensive care medicine. Transfusions. Cell therapy and gene therapy</subject><subject>Animals</subject><subject>Applied cell therapy and gene therapy</subject><subject>Biological and medical sciences</subject><subject>Biotechnology</subject><subject>Cardiomyocytes</subject><subject>Cell division</subject><subject>Cells, Cultured</subject><subject>Coronary artery</subject><subject>Cytokinesis</subject><subject>Endothelial Growth Factors - analysis</subject><subject>Endothelial Growth Factors - genetics</subject><subject>Fundamental and applied biological sciences. Psychology</subject><subject>Gene therapy</subject><subject>Gene transfer</subject><subject>Genetic Therapy - methods</subject><subject>Genetic Vectors - administration & dosage</subject><subject>Health. Pharmaceutical industry</subject><subject>Heart</subject><subject>Heart diseases</subject><subject>Immunohistochemistry</subject><subject>Industrial applications and implications. Economical aspects</subject><subject>Intercellular Signaling Peptides and Proteins - analysis</subject><subject>Intercellular Signaling Peptides and Proteins - genetics</subject><subject>Ischemia</subject><subject>Kinases</subject><subject>Lymphokines - analysis</subject><subject>Lymphokines - genetics</subject><subject>Medical sciences</subject><subject>Microscopy, Fluorescence</subject><subject>Mitosis</subject><subject>Models, Animal</subject><subject>Myocardial infarction</subject><subject>Myocardial ischemia</subject><subject>Myocardial Ischemia - therapy</subject><subject>Myocytes, Cardiac - metabolism</subject><subject>Myocytes, Cardiac - pathology</subject><subject>Occlusion</subject><subject>Protein kinase</subject><subject>Random Allocation</subject><subject>Reverse Transcriptase Polymerase Chain Reaction</subject><subject>Sus scrofa</subject><subject>Transfusions. Complications. Transfusion reactions. 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Economical aspects</topic><topic>Intercellular Signaling Peptides and Proteins - analysis</topic><topic>Intercellular Signaling Peptides and Proteins - genetics</topic><topic>Ischemia</topic><topic>Kinases</topic><topic>Lymphokines - analysis</topic><topic>Lymphokines - genetics</topic><topic>Medical sciences</topic><topic>Microscopy, Fluorescence</topic><topic>Mitosis</topic><topic>Models, Animal</topic><topic>Myocardial infarction</topic><topic>Myocardial ischemia</topic><topic>Myocardial Ischemia - therapy</topic><topic>Myocytes, Cardiac - metabolism</topic><topic>Myocytes, Cardiac - pathology</topic><topic>Occlusion</topic><topic>Protein kinase</topic><topic>Random Allocation</topic><topic>Reverse Transcriptase Polymerase Chain Reaction</topic><topic>Sus scrofa</topic><topic>Transfusions. Complications. Transfusion reactions. 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| subjects | Anesthesia. Intensive care medicine. Transfusions. Cell therapy and gene therapy Animals Applied cell therapy and gene therapy Biological and medical sciences Biotechnology Cardiomyocytes Cell division Cells, Cultured Coronary artery Cytokinesis Endothelial Growth Factors - analysis Endothelial Growth Factors - genetics Fundamental and applied biological sciences. Psychology Gene therapy Gene transfer Genetic Therapy - methods Genetic Vectors - administration & dosage Health. Pharmaceutical industry Heart Heart diseases Immunohistochemistry Industrial applications and implications. Economical aspects Intercellular Signaling Peptides and Proteins - analysis Intercellular Signaling Peptides and Proteins - genetics Ischemia Kinases Lymphokines - analysis Lymphokines - genetics Medical sciences Microscopy, Fluorescence Mitosis Models, Animal Myocardial infarction Myocardial ischemia Myocardial Ischemia - therapy Myocytes, Cardiac - metabolism Myocytes, Cardiac - pathology Occlusion Protein kinase Random Allocation Reverse Transcriptase Polymerase Chain Reaction Sus scrofa Transfusions. Complications. Transfusion reactions. Cell and gene therapy Vascular endothelial growth factor Vascular Endothelial Growth Factor A Vascular Endothelial Growth Factors |
| title | Entrance in mitosis of adult cardiomyocytes in ischemic pig hearts after plasmid-mediated rhVEGF165 gene transfer |
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