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Open AccessArticle

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

1
Laboratory of Angiopathology, Institute of General Pathology and Pathophysiology, 125315 Moscow, Russia
2
Laboratory of Medical Genetics, National Medical Research Center of Cardiology, 121552 Moscow, Russia
3
Plekhanov Russian University of Economics, 117997 Moscow, Russia
4
Department of Genetics, Southern Federal University, 344006 Rostov-on-Don, Russia
5
Institute for Atherosclerosis Research, Skolkovo Innovation Centre, 121609 Moscow, Russia
*
Author to whom correspondence should be addressed.
Biomolecules 2019, 9(9), 499; https://doi.org/10.3390/biom9090499
Received: 8 June 2019 / Revised: 5 September 2019 / Accepted: 11 September 2019 / Published: 18 September 2019
In the present work, a pilot creation of four cybrid cultures with high heteroplasmy level was performed using mitochondrial genome mutations m.12315G>A and m.1555G>A. According to data of our preliminary studies, the threshold heteroplasmy level of mutation m.12315G>A is associated with atherosclerosis. At the same time, for a mutation m.1555G>A, 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.12315G>A with the heteroplasmy level above the threshold value (25% and 44%, respectively) were obtained. In addition, two cybrid cell lines containing mutation m.1555G>A with a high heteroplasmy level (24%) were obtained. Cybrid cultures with mtDNA mutation m.12315G>A 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.1555G>A, it is possible to develop approaches to the gene therapy of atherosclerosis. View Full-Text
Keywords: cytoplasmatic hybrids; mitochondrial genome; mutation; gene; cybrids; mtDNA; therapy; cybrid model cytoplasmatic hybrids; mitochondrial genome; mutation; gene; cybrids; mtDNA; therapy; cybrid model
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Sazonova, M.A.; Sinyov, V.V.; Ryzhkova, A.I.; Sazonova, M.D.; Khasanova, Z.B.; Shkurat, T.P.; Karagodin, V.P.; Orekhov, A.N.; Sobenin, I.A. Creation of Cybrid Cultures Containing mtDNA Mutations m.12315G>A and m.1555G>A, Associated with Atherosclerosis. Biomolecules 2019, 9, 499.

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