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Zakirov FH, Zhang D, Grechko AV, Wu WK, Poznyak AV, Orekhov AN.

Pharmacol Res Perspect. 2020 Apr;8(2):e00584. doi: 10.1002/prp2.584.


Atherosclerosis with associated cardiovascular diseases remains one of the main causes of disability and death worldwide, requiring development of new solutions for prevention and treatment. Macrophages are the key effectors of a series of events involved in atherogenesis, such as inflammation, plaque formation, and changes in lipid metabolism. Some of these events were shown to be associated with mitochondrial dysfunction and excessive mitochondrial DNA (mtDNA) damage. Moreover, macrophages represent a promising target for novel therapeutic approaches that are based on the expression of various receptors and nanoparticle uptake. Lipid-based gene delivery to mitochondria is considered to be an interesting strategy for mtDNA damage correction. To date, several nanocarriers and their modifications have been developed that demonstrate high transfection efficiency and low cytotoxicity. This review discusses the possibilities of lipid-based gene delivery to macrophage mitochondria for atherosclerosis therapy.



atherosclerosis; gene delivery; liposomes; macrophages; mitochondrial dysfunction; mtDNA damage


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