The study "The role of genotoxic stress and DNA damage in the formation of endothelial dysfunction" was highly appreciated. The grant aims to study the molecular and genetic mechanisms of the formation of endothelial dysfunction caused by genotoxic stress in endothelial cells of the human coronary and internal thoracic arteries cultured under mutagenic load. 1.2 million rubles will be allocated for the implementation of the project during 2021-2022.
The approach proposed in the project is a pilot one: for the first time under conditions of induced mutagenesis, information will be obtained on the nature of changes in the expression of genes of key systems involved in the formation of endothelial dysfunction in cultures of endothelial cells of the coronary and internal thoracic arteries cultured under conditions of induced mutagenesis, as well as on the proteomic profile of these cells.
Currently, the contribution of somatic mutations to atherogenesis is actively discussed, and there are also studies showing that DNA damage, along with classical risk factors such as hypercholesterolemia, diabetes mellitus, smoking, and others, plays an important role in the development of endothelial dysfunction.
Understanding the molecular and genetic basis of the contribution of genotoxic stress to the development of endothelial dysfunction will make it possible to use DNA damage as a target for drugs in the treatment of atherosclerosis. It is also known that arteries of different diameters are susceptible to the development of atherosclerosis to varying degrees, while the mechanisms of this phenomenon are unknown. The study of the sensitivity of endothelial cells of arteries of different diameters to genotoxic effects and the nature of changes in their expression of genes involved in the pathogenesis of atherosclerosis will allow us to form an idea of the mechanisms of differential sensitivity of various arteries to atherosclerotic damage, which will also be used in the development of effective methods for the prevention and treatment of atherosclerosis.