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

Abstract

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.