Creation of Cybrid Cultures Containing mtDNA Mutations m.12315GA and m.1555GA, Associated with Atherosclerosis

摘要

In the present work, a pilot creation of four cybrid cultures with high heteroplasmy level was performed using mitochondrial genome mutations m.12315GA and m.1555GA. According to data of our preliminary studies, the threshold heteroplasmy level of mutation m.12315GA is associated with atherosclerosis. At the same time, for a mutation m.1555GA, such a heteroplasmy level is associated with the absence of atherosclerosis. Cybrid cultures were created by fusion of rho0-cells and mitochondria from platelets with a high heteroplasmy level of the investigated mutations. To create rho0-cells, THP-1 culture of monocytic origin was taken. According to the results of the study, two cybrid cell lines containing mutation m.12315GA with the heteroplasmy level above the threshold value (25% and 44%, respectively) were obtained. In addition, two cybrid cell lines containing mutation m.1555GA with a high heteroplasmy level (24%) were obtained. Cybrid cultures with mtDNA mutation m.12315GA can be used to model both the occurrence and development of atherosclerosis in cells and the titration of drug therapy for patients with atherosclerosis. With the help of cybrid cultures containing single nucleotide replacement of mitochondrial genome m.1555GA, it is possible to develop approaches to the gene therapy of atherosclerosis.