Potential use of buccal epithelium for genetic diagnosis of atherosclerosis using mtDNA mutations

Sinyov, Vasily V.; Sazonova, Margarita A.; Рыжкова, А.И.; Galitsyna, Elena V.; Melnichenko, Alexsandra A.; Postnov, Anton Y.; Orekhov, Alexander N.; Grechko, Andrey V.; Sobenin, Igor A.

doi:10.20517/2574-1209.2016.04

Cited by 27 publications

(25 citation statements)

References 13 publications

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“…Nevertheless, the results available to date position mitochondria as likely therapeutic targets for treatment of such diseases as cancer, chronic inflammatory states, and atherosclerosis. Selective mitochondria-targeting drugs, such as mitochondrial antioxidants, are being tested in preclinical and clinical trials [151,152]. Moreover, certain mtDNA mutations are being currently explored as diagnostic markers [152].…”

Section: Future Directionsmentioning

confidence: 99%

“…Selective mitochondria-targeting drugs, such as mitochondrial antioxidants, are being tested in preclinical and clinical trials [151,152]. Moreover, certain mtDNA mutations are being currently explored as diagnostic markers [152]. Future studies will improve our understanding of the mechanisms of mitochondrial involvement in the pathological processes.…”

Section: Future Directionsmentioning

confidence: 99%

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Possible Role of Mitochondrial DNA Mutations in Chronification of Inflammation: Focus on Atherosclerosis

Orekhov

Nikiforov

Ivanova

et al. 2020

JCM

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Chronification of inflammation is the process that lies at the basis of several human diseases that make up to 80% of morbidity and mortality worldwide. It can also explain a great deal of processes related to aging. Atherosclerosis is an example of the most important chronic inflammatory pathology in terms of public health impact. Atherogenesis is based on the inflammatory response of the innate immunity arising locally or focally. The main trigger for this response appears to be modified low-density lipoprotein (LDL), although other factors may also play a role. With the quick resolution of inflammation, atherosclerotic changes in the arterial wall do not occur. However, a violation of the innate immunity response can lead to chronification of local inflammation and, as a result, to atherosclerotic lesion formation. In this review, we discuss possible mechanisms of the impaired immune response with a special focus on mitochondrial dysfunction. Some mitochondrial dysfunctions may be due to mutations in mitochondrial DNA. Several mitochondrial DNA mutations leading to defective mitophagy have been identified. The regulatory role of mitophagy in the immune response has been shown in recent studies. We suggest that defective mitophagy promoted by mutations in mitochondrial DNA can cause innate immunity disorders leading to chronification of inflammation.

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Section: Future Directionsmentioning

confidence: 99%

Section: Future Directionsmentioning

confidence: 99%

Possible Role of Mitochondrial DNA Mutations in Chronification of Inflammation: Focus on Atherosclerosis

Orekhov

Nikiforov

Ivanova

et al. 2020

JCM

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“…On the opposite, the latest findings on the role of mitochondrial DNA variation in individual predisposition to atherosclerosis provide a growing body of evidence and the expectation of the breakthrough in understanding of molecular mechanisms and pathways of atherogenesis [14,15] . Heteroplasmic mtDNA mutations represent a promising molecular biomarker of genetic susceptibility to atherosclerosis and related pathologies [16][17][18][19] . In our study, we have demonstrated that several atherosclerosis-associated mutations of mitochondrial DNA taken together as a mutation burden of mitochondrial genome possess their own explanatory power and give a significant increase atop of assessment of conventional risk factors.…”

Section: Discussionmentioning

confidence: 99%

Profiling of risk of subclinical atherosclerosis: possible interplay of genetic and environmental factors as the update of conventional approach

Sobenin¹,

Myasoedova²,

Kirichenko³

et al. 2019

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Aim:To explore whether geographical location, genetic and environmental factors are associated with carotid atherosclerosis in high-risk individuals. Methods:In Moscow 470 apparently healthy, asymptomatic volunteer subjects with a high cardiovascular disease risk were recruited to participate in a cross-sectional study. Carotid intima-media thickness (cIMT), a validated biomarker for present and future cardiovascular disease risk, was assessed by means of high resolution ultrasound scans in subjects. Results:The total burden of conventional cardiovascular risk factors explained 21% of the cIMT variability; the mutational burden of mitochondrial genome defined by heteroplasmic mutations m.652delG, m.3256C>T, m.13513G>A, m.14459G>A, and m.15059G>A independently explained 23% variability; the combination of conventional and genetic risk factors increased explanatory level to 36%. Further exploratory statistical analyses showed air pollution as an independent risk factor for cIMT. Conclusion:In our study we confirmed and expanded the existence of a European geographic gradient of atherosclerosis risk and its association with cardiovascular disease risk. Geographical, environmental (particularly, air pollution) -and genetic risk factors (particularly, mutant variants of mitochondrial genome) may interplay in the formation of susceptibility to atherosclerosis.

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“…Mitochondrial dysfunction caused by mitochondrial DNA (mtDNA) damage is a well‐studied cause of cell dysfunction and death observed in atherosclerosis 7 . Correspondingly, dysfunctional mtDNA is regarded as a promising target for atherosclerosis treatment strategies.…”

Section: Introductionmentioning

confidence: 99%

Lipid‐based gene delivery to macrophage mitochondria for atherosclerosis therapy

Zakirov

Zhang

Grechko

et al. 2020

Pharmacology Res & Perspec

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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.

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Potential use of buccal epithelium for genetic diagnosis of atherosclerosis using mtDNA mutations

Cited by 27 publications

References 13 publications

Possible Role of Mitochondrial DNA Mutations in Chronification of Inflammation: Focus on Atherosclerosis

Possible Role of Mitochondrial DNA Mutations in Chronification of Inflammation: Focus on Atherosclerosis

Profiling of risk of subclinical atherosclerosis: possible interplay of genetic and environmental factors as the update of conventional approach

Lipid‐based gene delivery to macrophage mitochondria for atherosclerosis therapy

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