Intramyocardial Injection of Plasmid Encoding Platelet Growth Factor Increases Epicardial-Mediated Post Infarction Myocardial Vascularization (Experimental Study)

Increasing incidence of ischemic diseases and limited resources for their treatment stimulate increased interest in studying the mechanisms of vascularization and finding new approaches for its promotion. One of these approaches is gene therapy aimed at activating the epicardium to produce the vascu...

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Main Authors: K. V. Dergilev, Z. I. Tsokolaeva, I. B. Beloglazova, D. O. Traktuev, A. V. Gorelova, А. V. Zubko, B. N. Kulbitsky, Е. V. Parfenova
Format: Article
Language:English
Published: Federal Research and Clinical Center of Intensive Care Medicine and Rehabilitology, Moscow, Russia 2020-12-01
Series:Общая реаниматология
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Online Access:https://www.reanimatology.com/rmt/article/view/1986
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author K. V. Dergilev
Z. I. Tsokolaeva
I. B. Beloglazova
D. O. Traktuev
A. V. Gorelova
А. V. Zubko
B. N. Kulbitsky
Е. V. Parfenova
author_facet K. V. Dergilev
Z. I. Tsokolaeva
I. B. Beloglazova
D. O. Traktuev
A. V. Gorelova
А. V. Zubko
B. N. Kulbitsky
Е. V. Parfenova
author_sort K. V. Dergilev
collection DOAJ
description Increasing incidence of ischemic diseases and limited resources for their treatment stimulate increased interest in studying the mechanisms of vascularization and finding new approaches for its promotion. One of these approaches is gene therapy aimed at activating the epicardium to produce the vascular precursor cells and microenvironment for the «assembly» of de novo vessels.The aim is to investigate the possibility of activating epicardial cells and post infarction cardiac vascularization by injecting a genetic construct encoding PDGFBB.Material and methods. A model of experimental myocardial infarction in a rat with subsequent intramyocardial injection of normal saline solution, control plasmid and plasmid encoding PDGFBB was used. The study of PDGFBB effect on epicardial cell activity was performed on the ex vivo model, as well as in vitro mesothelial cell culture.Results. Post infarction injection of plasmid encoding PDGFBB increases the density of the vascular network in the peri-infarct area as well as migration of pericytes to the injured zone. PDGFBB promotes activation of epicardial cell pool and expression of smooth muscle cell markers in them (shown on the ex vivo model), as well as stimulates activation of epithelial-mesenchymal transition (in vitro).Conclusion. Intramyocardial injection of a genetic construct encoding PDGFBB after an experimental myocardial infarction stimulated vascularization of the peri-infarction zone, which may have been partially due to the activation of the epicardial cell pool.
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spelling doaj.art-fabc73a3d82c4127814e8305ec425a692023-03-13T09:32:56ZengFederal Research and Clinical Center of Intensive Care Medicine and Rehabilitology, Moscow, RussiaОбщая реаниматология1813-97792411-71102020-12-01166546410.15360/1813-9779-2020-6-54-641769Intramyocardial Injection of Plasmid Encoding Platelet Growth Factor Increases Epicardial-Mediated Post Infarction Myocardial Vascularization (Experimental Study)K. V. Dergilev0Z. I. Tsokolaeva1I. B. Beloglazova2D. O. Traktuev3A. V. Gorelova4А. V. Zubko5B. N. Kulbitsky6Е. V. Parfenova7Институт экспериментальной кардиологиимНационального медицинского исследовательского центра кардиологии Минздрава РоссииИнститут экспериментальной кардиологии Национального медицинского исследовательского центра кардиологии Минздрава России; НИИ общей реаниматологии им. В.А. Неговского ФНКЦ РРИнститут экспериментальной кардиологиимНационального медицинского исследовательского центра кардиологии Минздрава РоссииНИИ общей реаниматологии им. В.А. Неговского ФНКЦ РРЦентр регенеративной медицины, Медицинское отделение, Медицинский колледж, Университет Флориды; Университет Манчестера, Факультет Биологии, Медицины и ЗдоровьяНациональный медицинский научно-исследовательский центр сердечно-сосудистой хирургии им. Бакулева Минздрава РоссииГоспиталь для ветеранов войн № 3, Департамент здравоохранения г. МосквыИнститут экспериментальной кардиологиимНационального медицинского исследовательского центра кардиологии Минздрава РоссииIncreasing incidence of ischemic diseases and limited resources for their treatment stimulate increased interest in studying the mechanisms of vascularization and finding new approaches for its promotion. One of these approaches is gene therapy aimed at activating the epicardium to produce the vascular precursor cells and microenvironment for the «assembly» of de novo vessels.The aim is to investigate the possibility of activating epicardial cells and post infarction cardiac vascularization by injecting a genetic construct encoding PDGFBB.Material and methods. A model of experimental myocardial infarction in a rat with subsequent intramyocardial injection of normal saline solution, control plasmid and plasmid encoding PDGFBB was used. The study of PDGFBB effect on epicardial cell activity was performed on the ex vivo model, as well as in vitro mesothelial cell culture.Results. Post infarction injection of plasmid encoding PDGFBB increases the density of the vascular network in the peri-infarct area as well as migration of pericytes to the injured zone. PDGFBB promotes activation of epicardial cell pool and expression of smooth muscle cell markers in them (shown on the ex vivo model), as well as stimulates activation of epithelial-mesenchymal transition (in vitro).Conclusion. Intramyocardial injection of a genetic construct encoding PDGFBB after an experimental myocardial infarction stimulated vascularization of the peri-infarction zone, which may have been partially due to the activation of the epicardial cell pool.https://www.reanimatology.com/rmt/article/view/1986инфаркт миокардаклетки эпикардафактор роста тромбоцитовваскуляризациярепарация сердца
spellingShingle K. V. Dergilev
Z. I. Tsokolaeva
I. B. Beloglazova
D. O. Traktuev
A. V. Gorelova
А. V. Zubko
B. N. Kulbitsky
Е. V. Parfenova
Intramyocardial Injection of Plasmid Encoding Platelet Growth Factor Increases Epicardial-Mediated Post Infarction Myocardial Vascularization (Experimental Study)
Общая реаниматология
инфаркт миокарда
клетки эпикарда
фактор роста тромбоцитов
васкуляризация
репарация сердца
title Intramyocardial Injection of Plasmid Encoding Platelet Growth Factor Increases Epicardial-Mediated Post Infarction Myocardial Vascularization (Experimental Study)
title_full Intramyocardial Injection of Plasmid Encoding Platelet Growth Factor Increases Epicardial-Mediated Post Infarction Myocardial Vascularization (Experimental Study)
title_fullStr Intramyocardial Injection of Plasmid Encoding Platelet Growth Factor Increases Epicardial-Mediated Post Infarction Myocardial Vascularization (Experimental Study)
title_full_unstemmed Intramyocardial Injection of Plasmid Encoding Platelet Growth Factor Increases Epicardial-Mediated Post Infarction Myocardial Vascularization (Experimental Study)
title_short Intramyocardial Injection of Plasmid Encoding Platelet Growth Factor Increases Epicardial-Mediated Post Infarction Myocardial Vascularization (Experimental Study)
title_sort intramyocardial injection of plasmid encoding platelet growth factor increases epicardial mediated post infarction myocardial vascularization experimental study
topic инфаркт миокарда
клетки эпикарда
фактор роста тромбоцитов
васкуляризация
репарация сердца
url https://www.reanimatology.com/rmt/article/view/1986
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