Approaches to the gene therapeutic correction of the pathogenetic mechanisms of coronary insufficiency
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The absence of neoangiogenesis in the ischemic myocardium is the reason for the widespread prevalence of cardiovascular diseases. The mechanism is the age-dependent epigenetic blockade of the corresponding genes. In model experiments, it was shown that transfection of ischemic myocardium with plasmid vectors carrying the HIF1a, HIF1b, VEGF165, VEGF225 genes in a stoichiometric ratio of 1: 0.2: 0.5: 0.3, at a concentration of 400 μg / ml of physiological solution at a rate of 200 μg DNA per cm2 of ischemia zone and a step over an area of 2-10 mm, with the addition of an adjuvant2-dimethylaminoethanol at a concentration of 2.5 mmol / L, restores full neoangiogenesis. For the first time, it was shown that as a result of gene therapy of myocardial ischemia using four genes (HIF-1α, HIF-1β, VEGF 225, VEGF 165).In contrast to the known monotherapy methods, a complete vascular network is formed in the ischemic zone, having anatamoses with intact vessels. The scientific novelty of the study lies in the fact that the obtained data open the possibility of correction of epigenetic blocking of gene expression by transfecting cells with copies of these genes without epigenetic labels.
Oleg. G. Makeev, Evgeny A. Shuman, Arteom V. Korotkov, Svetlana. V. Kostyukova. Approaches to the gene therapeutic correction of the pathogenetic mechanisms of coronary insufficiency. Cardiometry; Issue 17; November 2020; p.66-75; DOI: 10.12710/cardiometry.2020.17.6675; Available from: http://www.cardiometry.net/issues/no17-november-2020/gene-therapeutic-correction