Mitochondrial mutations associated with cardiac angina

Рыжкова, А.И.; Sinyov, Vasily V.; Sazonova, Margarita A.; Nikitina, N.A.; Шкурат, Т. П.; Sobenin, Igor A.; Orekhov, Alexander N.

doi:10.20517/2574-1209.2019.01

Cited by 6 publications

(7 citation statements)

References 19 publications

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“…Their prevalence is affected by various factors, such as sex and regional location [64,[69][70][71] . Whole blood cells and buccal epithelial cells are used as biomarkers of mitochondrial mutations associated with atherosclerosis [72][73][74] . The detection of threshold heteroplasmy levels of mtDNA mutations, above which patients are at increased risk of atherosclerotic progression, may be a new assessment criterion for the occurrence and development of atherosclerotic lesions in human arteries [73,75] .…”

Section: Mitochondrial Dna Mutation Is Associated With Atherosclerosi...mentioning

confidence: 99%

Challenges of mitochondrial DNA editing in mammalian cells: focus on treatment of cardiovascular disease

2022

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Atherosclerosis is the major cause of occurrence and development of cardiovascular disease. Mutations in mitochondrial DNA (mtDNA) can lead to the development of several pathologies. Over the last few years, there has been increasing evidence that mitochondrial dysfunction caused by mtDNA mutations is associated with atherogenesis and other diseases of the cardiovascular system. Several therapeutic approaches have been developed for the improvement of mitochondrial function, and they are mainly associated with the cellular and tissue antioxidant defense system. However, these approaches are not targeted at mtDNA mutations, which trigger the pathogenesis of disease. Gene-editing technologies could be a promising approach for the treatment of cardiovascular disease caused by mtDNA mutations. To date, such technologies have shown considerable success in mitochondrial gene editing in cell and animal models. Gene-editing technologies allow the determination of the role of mitochondrial genome mutations in the development and complication of various chronic diseases. Nevertheless, further investigation and optimization in this field is required for future human trials. This review highlights the progress and existing challenges of modern technologies and approaches to mitochondrial gene editing.

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Section: Mitochondrial Dna Mutation Is Associated With Atherosclerosi...mentioning

confidence: 99%

Challenges of mitochondrial DNA editing in mammalian cells: focus on treatment of cardiovascular disease

2022

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“…Most of mutations, linked with atherosclerosis, cardiovascular diseases and aging, belong to genes of subunits of mitochondrial respiratory chain enzymes ( MT-ND1 , MT-ND2 , MT-ND5 , MT-ND6 , MT-CYTB ) [ 18 , 235 , 245 , 246 , 247 , 248 , 249 ]. The occurrence of such mutations can lead to energy deficiency in cells, for the reason of enzyme dysfunction [ 18 , 235 , 245 , 246 , 247 , 248 ]. This, in its turn, can lead to mitochondrial dysfunction and oxidative stress in cells and in the human organism.…”

Section: The Relationship Of Chronic Stress With the Occurrence Anmentioning

confidence: 99%

Some Molecular and Cellular Stress Mechanisms Associated with Neurodegenerative Diseases and Atherosclerosis

Sinyov

Рыжкова

Sazonova

et al. 2021

IJMS

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Chronic stress is a combination of nonspecific adaptive reactions of the body to the influence of various adverse stress factors which disrupt its homeostasis, and it is also a corresponding state of the organism’s nervous system (or the body in general). We hypothesized that chronic stress may be one of the causes occurence of several molecular and cellular types of stress. We analyzed literary sources and considered most of these types of stress in our review article. We examined genes and mutations of nuclear and mitochondrial genomes and also molecular variants which lead to various types of stress. The end result of chronic stress can be metabolic disturbance in humans and animals, leading to accumulation of reactive oxygen species (ROS), oxidative stress, energy deficiency in cells (due to a decrease in ATP synthesis) and mitochondrial dysfunction. These changes can last for the lifetime and lead to severe pathologies, including neurodegenerative diseases and atherosclerosis. The analysis of literature allowed us to conclude that under the influence of chronic stress, metabolism in the human body can be disrupted, mutations of the mitochondrial and nuclear genome and dysfunction of cells and their compartments can occur. As a result of these processes, oxidative, genotoxic, and cellular stress can occur. Therefore, chronic stress can be one of the causes forthe occurrence and development of neurodegenerative diseases and atherosclerosis. In particular, chronic stress can play a large role in the occurrence and development of oxidative, genotoxic, and cellular types of stress.

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“…Созданные цибридные культуры несут мутацию, локализованную в кодирующем регионе митохондриального генома [11,[27][28][29][30]. Мутация m.12315G>A локализована в гене MT-TL2.…”

Section: результаты и обсуждениеunclassified

Creation of cybrid cell cultures containing a single-nucleotide substitution associated with atherosclerosis in the MT-TL2 gene

Синёв¹,

Рыжкова²,

Sazonova³

et al. 2020

Zhurnal «Patologicheskaia Fiziologiia I Eksperimental`naia Terapiia»

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Введение. Цибридные клеточные модели наиболее перспективны для изучения патогенеза различных заболеваний. Авторами статьи впервые были созданы такие модели для изучения митохондриальной дисфункции и патологических процессов, развивающихся при атеросклерозе. Цель работы - создание цибридных культур с высоким уровнем гетероплазмии по мутации митохондриального генома m.12315G>A. В предварительных исследованиях авторами статьи было установлено, что пороговый уровень гетероплазмии мутации m.12315G>A ассоциирован с атеросклерозом. Методика. Цибридные культуры создавали путем слияния безмитохондриальных клеток (rho0) и митохондрий из тромбоцитов участников исследования с высоким уровнем гетероплазмии исследуемых мутаций. Для создания rho0-клеток была взята культура моноцитарного происхождения THP-1. Безмитохондриальные клетки были получены с помощью метода M. Kинга и Г. Аттарди. Тромбоциты выделяли из цельной крови участников исследования. Для этого был применен метод центрифугирования в градиенте плотности фиколла-урографина. Для получения цибридных культур клеток была использована методика «ПЭГ-слияния». В созданных безмитохондриальных и цибридных клеточных культурах был проведен количественный анализ копий митохондриального генома. Согласно результатам данного анализа было подтверждено либо отсутствие митохондрий (rho0-клетки), либо их наличие (цибриды). Количество копий мтДНК детектировалось с помощью реал-тайм ПЦР в присутствии красителя SYBR Green I. Результаты. Получены 4 цибридные клеточные линии, содержащие мутацию m.12315G>A с уровнем гетероплазмии выше порогового значения. Заключение. Созданы 4 цибридные культуры с высоким уровнем гетероплазмии по мутации митохондриального генома m.12315G>A. Полученные цибридные клеточные линии могут служить моделями для изучения молекулярно-клеточных механизмов митохондриальной дисфункции при атеросклерозе и других сердечно-сосудистых заболеваниях. Цибридные культуры можно использовать для моделирования атерогенеза, а также для подбора патогенетически обоснованной лекарственной терапии при атеросклерозе. Introduction. Cybrid cell models are most promising for studying pathological mechanisms in different diseases. The authors for the first time created such models for studying mitochondrial dysfunction and pathological processes underlying atherosclerosis. Aim. Creation of cybrid cultures with a high heteroplasmy level for mitochondrial genome mutation m.12315G>A. A preliminary study by the authors showed that the heteroplasmy level of mutation m.12315G>A was associated with atherosclerosis. Methods. Cybrid cultures were created by fusing non-mitochondrial cells (rho0) and mitochondria from platelets of study participants with a high heteroplasmy level of the mutations under study. A THP-1 culture of monocytic origin was used to create rho0 cells. Non-mitochondrial cells were obtained using the M. King and G. Attardi method. Platelets were extracted from whole blood of study participants with Ficoll-Urografin density gradient centrifugation. Cybrid cell cultures were obtained by the PEG-mediated fusion method. In the created non-mitochondrial and cybrid cell cultures, quantitative analysis of mitochondrial genome copies was performed. This analysis confirmed either the absence of mitochondria (rho0-cells) or their presence (cybrids). The mtDNA copies were quantified using real-time PCR in the presence of the SYBR Green I stain. Results. Four cybrid cell lines were obtained, which contained the m.12315G>A mutation with heteroplasmy levels higher than the threshold level. Conclusion. Four cybrid cultures were created with a high heteroplasmy level for the mitochondrial genome mutation m.12315G>A. The obtained cell lines can be used as models for studying molecular cellular mechanisms of mitochondrial dysfunction in atherosclerosis and cardiovascular diseases. In addition, they may be useful for modeling atherogenesis in cells and for selecting therapy for patients with atherosclerosis.

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Mitochondrial mutations associated with cardiac angina

Cited by 6 publications

References 19 publications

Challenges of mitochondrial DNA editing in mammalian cells: focus on treatment of cardiovascular disease

Challenges of mitochondrial DNA editing in mammalian cells: focus on treatment of cardiovascular disease

Some Molecular and Cellular Stress Mechanisms Associated with Neurodegenerative Diseases and Atherosclerosis

Creation of cybrid cell cultures containing a single-nucleotide substitution associated with atherosclerosis in the MT-TL2 gene

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