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Page 4 of 6 Sobenin. Vessel Plus 2020;4:18 I http://dx.doi.org/10.20517/2574-1209.2020.09

mitochondria, thus playing a pathogenic role in the formation of atherosclerotic lesions. The decrease in
concentration of these enzymes and tRNAs in mitochondria, and the resulting mitochondrial dysfunction
[25]
contributes to oxidative stress, deterioration of ATP production and acceleration of atherogenesis .
Recently we have performed a series of studies on the relationships between (1) mtDNA variability and
the changes in cellular composition of arterial atherosclerotic intima and the expression of apoptosis- and
inflammation-related genes; (2) mtDNA variants, carotid atherosclerosis and conventional cardiovascular
risk factors; and (3) individual mtDNA mutation burden and functional activity of cells in cell culture
studies. The results of these studies strongly support the hypothesis on the atherogenic role of mtDNA
mutations [26,27] . In further studies, we aimed to create cell models that reproduce the pathological cellular
atherosclerotic phenotype with the use of promising approaches such as cytoplasmic hybrids (cybrids). At
this stage of our studies, we have demonstrated that cybrid cells obtained from the homogeneous THP-1
line acquire completely different functional properties, and these changes were due solely to the functional
activity of the donor mitochondria and the properties and mutational load of the introduced donor’s
mtDNA [28,29] . However, the effects observed in cybrid cell lines are dependent not on some specific mtDNA
variant, but on a unique combination of variants due to extremely high individual variation. Therefore,
we needed more precise cellular models to investigate the intrinsic molecular mechanisms, which may
be involved in the formation of the atherosclerotic phenotype due to mtDNA mutations; the use of direct
mtDNA editing seemed plausible. We have launched a new research project, which would consistently
carry out the design of liposomal delivery of nucleic acids and antisense RNA into cells and further
into mitochondria, the delivery of CAS9 nuclease, sgRNA and ssODN recombination matrix, for the
[30]
implementation of point mutations in mitochondrial genes . This approach was approved and supported
by the Russian Science Foundation. Currently, we have developed cationic liposomes with different
addressable modules, evaluated the ability to deliver DNA and to transfect a vector expressing GFP into
cells, developed the specific vector for introducing double-stranded breaks in mitochondrial genes, and for
[30]
visualization of CAS9 localization in mitochondria . These studies will help to evaluate the pathogenic
role of deleterious mtDNA mutations in the formation of atherosclerotic phenotypes at the cellular level,
and to find novel molecular targets for the prevention and treatment of atherosclerotic pathology.

In conclusion, I would like to thank the scientists and researchers who have contributed to this special issue
of “Vessel Plus” and shared their own thoughts on recent fundamental, generalized and clinical findings, all
of which are aimed at evaluating atherosclerosis-related and metabolic pathologies [31-34] .

DECLARATIONS
Authors’ contributions
The author contributed solely to the article.

Availability of data and materials
Not applicable.

Financial support and sponsorship
This work was supported in part by Russian Science Foundation, Grant No. 19-15-00297.

Conflicts of interest
The author declared that there are no conflicts of interest.

Ethical approval and consent to participate
Not applicable.