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1.
Biomol Concepts ; 12(1): 55-67, 2021 Jun 11.
Artigo em Inglês | MEDLINE | ID: mdl-34115932

RESUMO

Abdominal aortic aneurysm (AAA) is a complex degenerative vascular disease, with considerable morbidity and mortality rates among the elderly population. The mortality of AAA is related to aneurysm expansion (the enlargement of the aortic diameter up to 30 mm and above) and the subsequent rupture. The pathogenesis of AAA involves several biological processes, including aortic mural inflammation, oxidative stress, vascular smooth muscle cell apoptosis, elastin depletion, and degradation of the extracellular matrix. Mitochondrial dysfunction was also found to be associated with AAA formation. The evidence accumulated to date supports a close relationship between environmental and genetic factors in AAA initiation and progression. However, a comprehensive pathophysiological understanding of AAA formation remains incomplete. The open surgical repair of AAA is the only therapeutic option currently available, while a specific pharmacotherapy is still awaited. Therefore, there is a great need to clarify pathophysiological cellular and molecular mechanisms underlying AAA formation that would help to develop effective pharmacological therapies. In this review, pathophysiological aspects of AAA development with a special focus on mitochondrial dysfunction and genetic associations were discussed.

2.
Int J Mol Sci ; 22(8)2021 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-33920897

RESUMO

In this Special Issue of the International Journal of Molecular Sciences, we include insightful reviews and research papers on the subject "Immunopathology of Atherosclerosis and Related Diseases: Focus on Molecular Biology".[...].


Assuntos
Aterosclerose/imunologia , Aterosclerose/patologia , Biologia Molecular , Alarminas/metabolismo , Evolução Biológica , DNA Mitocondrial/metabolismo , Humanos , Imunidade Inata , Inflamação/patologia , Microbiota , Modelos Biológicos
3.
Toxicol Rep ; 8: 499-504, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33732625

RESUMO

Aim: The aim of this work was to study the effect of telomere length in the chromosomes of nuclear blood cells in individuals with coronary heart disease (CHD) on the development of cardiovascular complications (CVC). Materials and methods: DNA was isolated from nuclear blood cells of 498 study participants. The telomere length was determined by real-time polymerase chain reaction. The investigation of each sample was repeated three times. Five years after the end of this study, a telephone survey of 119 patients with CHD was conducted in order to obtain data on the presence of CVC. Results: According to the results obtained, a decrease in telomere length in patients with coronary heart disease increases the risk of subsequent development of cardiovascular complications. Conclusion: Patients with coronary heart disease with shorter telomeres compared with conventionally healthy study participants had an increased risk of cardiovascular complications within 5 years after telomere analysis.

4.
Int J Mol Sci ; 22(2)2021 Jan 12.
Artigo em Inglês | MEDLINE | ID: mdl-33445687

RESUMO

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.


Assuntos
Aterosclerose/metabolismo , Aterosclerose/patologia , Doenças Neurodegenerativas/metabolismo , Doenças Neurodegenerativas/patologia , Estresse Oxidativo/fisiologia , Animais , Homeostase/fisiologia , Humanos , Mitocôndrias/metabolismo , Mitocôndrias/patologia , Espécies Reativas de Oxigênio/metabolismo
6.
Curr Med Chem ; 28(12): 2438-2450, 2021 May 04.
Artigo em Inglês | MEDLINE | ID: mdl-32867633

RESUMO

The most typical feature of atherogenesis in humans at its early stage is the formation of foam cells in subendothelial arterial intima, which occurs as the consequence of intracellular cholesterol deposition. The main source of lipids accumulating in the arterial wall is circulating low-density lipoprotein (LDL). However, LDL particles should undergo proatherogenic modification to acquire atherogenic properties. One of the known types of atherogenic modification of LDL is enzymatic deglycosilation, namely, desialylation, which is the earliest change in the cascade of following multiple LDL modifications. The accumulating data make sialidases an intriguing and plausible therapeutic target, since pharmacological modulation of activity of these enzymes may have beneficial effects in several pathologies, including atherosclerosis. The hypothesis exists that decreasing LDL enzymatic desialylation may result in the prevention of lipid accumulation in arterial wall, thus breaking down one of the key players in atherogenesis at the cellular level. Several drugs acting as glycomimetics and inhibiting sialidase enzymatic activity already exist, but the concept of sialidase inhibition as an anti-atherosclerosis strategy remains unexplored to date. This review is focused on the potential possibilities of the repurposing of sialidase inhibitors for pathogenetic anti-atherosclerotic therapy.


Assuntos
Aterosclerose , Neuraminidase , Aterosclerose/tratamento farmacológico , Inibidores Enzimáticos/uso terapêutico , Humanos , Lipoproteínas LDL
7.
Curr Pharm Des ; 27(2): 177-184, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-32867647

RESUMO

BACKGROUND: The present review article considers some chronic diseases of vascular and metabolic genesis, the causes of which may be mitochondrial dysfunction. Very often, in the long course of the disease, complications may occur, leading to myocardial infarction or ischemic stroke and, as a result, death. In particular, a large percentage of human deaths nowadays belongs to cardiovascular diseases, such as coronary heart disease (CHD), arterial hypertension, cardiomyopathies, and type 2 diabetes mellitus. OBJECTIVE: The aim of the present review was the analysis of literature sources, devoted to an investigation of a link of mitochondrial DNA mutations with chronic diseases of vascular and metabolic genesis. RESULTS: The analysis of literature indicates the association of the mitochondrial genome mutations with coronary heart disease, type 2 diabetes mellitus, hypertension, and various types of cardiomyopathies. CONCLUSION: The detected mutations can be used to analyze the predisposition to chronic diseases of vascular and metabolic genesis. They can also be used to create molecular-cell models necessary to evaluate the effectiveness of drugs developed for the treatment of these pathologies. MtDNA mutations associated with the absence of diseases of vascular and metabolic genesis could be potential candidates for gene therapy of the said diseases.


Assuntos
Diabetes Mellitus Tipo 2 , Hipertensão , DNA Mitocondrial/genética , Diabetes Mellitus Tipo 2/genética , Humanos , Mitocôndrias/genética , Mutação
8.
Am J Cardiovasc Dis ; 10(4): 463-472, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33224597

RESUMO

Background: It is well-known that the distribution of traditional cardiovascular risk factors (CVRFs) of atherosclerosis, including hypertension, dyslipidemia, smoking, obesity, and diabetes is considerably variable between different countries, however, with some important geographical trends. Thus, CVRFs contribute differently to atherosclerosis development in different countries. Common carotid artery intima-media thickness (CCA IMT) is a validated biomarker of subclinical atherosclerosis that is used in clinical and epidemiological studies to evaluate the impact of CVRFs on atherosclerosis development. Material and methods: This comparative cohort study included a random sample of 1200 participants (n = 600 men and n = 600 women) from Moscow, Russia and Paris, France, aged between 55 and 79 years, and free of clinical symptoms of atherosclerosis. The study was conducted to determine the interpopulation variability of CCA IMT. CCA IMT was measured by ultrasonic scanning at the high-resolution regimen. Statistical analysis was performed using Stata 9.1. For comparison of mean values of continuous variables, Mann-Whitney U-test was used; Chi-square, Pearson's test was used for comparison of categorical variables. To determine to what extent presented differences can be explained by differences in traditional CVRFs, the regression model was applied. Path analysis (plug Passport Litigation Decision Analysis & Optimization Module, Datacert, USA) was used to assess the impact of traditional CVRFs on the CCA IMT in both Moscow and Paris study populations. Results: There was a significant difference in the distribution of most of the traditional CVRFs between the study populations, including blood pressure, lipid profile, statin treatment, hormone replacement therapy in women, and CVD history. The remarkably high level of difference in the mean values of the CCA IMT was found between Moscow and Paris study populations. In women of both Moscow and Paris study populations, the mean value of CCA IMT was 0.78 and 0.63, respectively. In men of both Moscow and Paris study populations, the mean CCA IMT value was 0.84 and 0.67, respectively. In the Moscow study population, the effects (direct and indirect) of traditional CVRs can explain 42% of the CCA IMT variance in women and 30% - in men. In the Paris study population, direct and indirect effects of traditional CVRFs can explain 27% of the CCA IMT variance in men and 14% - in women. Conclusion: The Paris study population significantly differed from the Moscow study population in the distribution and impact of traditional CVRFs. Traditional CVRFs can explain only a small proportion of the interpopulation differences in CCA IMT suggesting the presence of other factors, such as longitude, which can possibly influence these differences. Therefore, this study provided an additional piece of evidence towards the existence of a geographic gradient of carotid IMT.

9.
Antioxidants (Basel) ; 9(11)2020 Nov 19.
Artigo em Inglês | MEDLINE | ID: mdl-33228202

RESUMO

Abdominal aortic aneurysm (AAA) and intracranial aneurysm (IA) are serious arterial diseases in the aorta and brain, respectively. AAA and IA are associated with old age in males and females, respectively, and if rupture occurs, they carry high morbidity and mortality. Aneurysmal subarachnoid hemorrhage (SAH) due to IA rupture has a high rate of complication and fatality. Despite these severe clinical outcomes, preventing or treating these devastating diseases remains an unmet medical need. Inflammation and oxidative stress are shared pathologies of these vascular diseases. Therefore, therapeutic strategies have focused on reducing inflammation and reactive oxygen species levels. Interestingly, in response to cellular stress, the inducible heme oxygenase-1 (HO-1) is highly upregulated and protects against tissue injury. HO-1 degrades the prooxidant heme and generates molecules with antioxidative and anti-inflammatory properties, resulting in decreased oxidative stress and inflammation. Therefore, increasing HO-1 activity is an attractive option for therapy. Several HO-1 inducers have been identified and tested in animal models for preventing or alleviating AAA, IA, and SAH. However, clinical trials have shown conflicting results. Further research and the development of highly selective HO-1 regulators may be needed to prevent the initiation and progression of AAA, IA, or SAH.

10.
J Pers Med ; 10(4)2020 Oct 02.
Artigo em Inglês | MEDLINE | ID: mdl-33023269

RESUMO

This study is aimed at investigating the relationship between inflammation, the number of vasa vasorum, and the presence of lipoprotein (a) [Lp(a)] in the aortic aneurysm wall, as well as the relationships of these pathological processes with the development of aneurysm wall dissection. To that end, we examined segments of aortic aneurysm wall, consisting of intima, media, and adventitia, collected from patients during aneurysm prosthetics intervention. The material was collected from 23 men and eight women aged from 33 to 69 years. Monoclonal antibodies to Lp(a), markers of monocytes and macrophages (CD68), T cells (CD3, CD4, and CD8), von Willebrand factor, endothelium NO synthase, and smooth muscle α-actin were used for morphological and morphometric investigation. The present study demonstrated that Lp(a) is not often found in biopsies of patients with thoracic aortic aneurysm. Morphological and morphometric investigation shows the connection of aortic dissection with the process of damage to its wall caused by inflammatory infiltrates, medianecroses, and the appearance of newly formed vasa vasorum in media.

11.
Curr Atheroscler Rep ; 22(10): 54, 2020 08 09.
Artigo em Inglês | MEDLINE | ID: mdl-32772280

RESUMO

PURPOSE OF REVIEW: Mutations in both nuclear and mitochondrial genes are associated with the development of atherosclerotic lesions in arteries and may provide a partial explanation to the focal nature of lesion distribution in the arterial wall. This review is aimed to discuss the genetic aspects of atherogenesis with a special focus on possible pro-atherogenic variants (mutations) of the nuclear and mitochondrial genomes that may be implicated in atherosclerosis development and progression. RECENT FINDINGS: Mutations in the nuclear genes generally do not cause a phenotype restricted to a specific vascular wall cell and manifest themselves mostly at the organism level. Such mutations can act as important contributors to changes in lipid metabolism and modulate other risk factors of atherosclerosis. By contrast, mitochondrial DNA (mtDNA) mutations occurring locally in the arterial wall cells or in circulating immune cells may play a site-specific role in atherogenesis. The mosaic distribution of heteroplasmic mtDNA mutations in the arterial wall tissue may explain, at least to some extent, the locality and focality of atherosclerotic lesions distribution. The genetic mechanisms of atherogenesis include alterations of both nuclear and mitochondrial genomes. Altered lipid metabolism and inflammatory response of resident arterial wall and circulating immune cells may be related to mtDNA damage and defective mitophagy, which hinders clearance of dysfunctional mitochondria. Mutations of mtDNA can have mosaic distribution and locally affect functionality of endothelial and subendothelial intimal cells in the arterial wall contributing to atherosclerotic lesion development.


Assuntos
Aterosclerose/genética , Mitocôndrias/genética , Mutação , Animais , Artérias/metabolismo , Artérias/patologia , Aterosclerose/metabolismo , DNA Mitocondrial/genética , DNA Mitocondrial/metabolismo , Genoma Mitocondrial , Humanos , Fenótipo , Polimorfismo de Nucleotídeo Único
12.
Int J Mol Sci ; 21(15)2020 Jul 31.
Artigo em Inglês | MEDLINE | ID: mdl-32751832

RESUMO

Immunoglobulins are the potent effector proteins of the humoral immune response. In the course of evolution, immunoglobulins have formed extremely diverse types of molecular structures with antigen-recognizing, antigen-binding, and effector functions embedded in a single molecule. Polysaccharide moiety of immunoglobulins plays the essential role in immunoglobulin functioning. There is growing evidence that the carbohydrate composition of immunoglobulin-linked glycans, and especially their terminal sialic acid residues, provide a key effect on the effector functions of immunoglobulins. Possibly, sialylation of Fc glycan is a common mechanism of IgG anti-inflammatory action in vivo. Thus, the post-translational modification (glycosylation) of immunoglobulins opens up significant possibilities in the diagnosis of both immunological and inflammatory disorders and in their therapies. This review is focused on the analysis of glycosylation of immunoglobulins, which can be a promising addition to improve existing strategies for the diagnosis and treatment of various immuno-inflammatory diseases.


Assuntos
Doenças do Sistema Imunitário/tratamento farmacológico , Fragmentos Fc das Imunoglobulinas/química , Imunoglobulina G , Inflamação/tratamento farmacológico , Ácido N-Acetilneuramínico/química , Polissacarídeos/química , Animais , Glicosilação , Humanos , Imunoglobulina G/química , Imunoglobulina G/uso terapêutico , Camundongos , Processamento de Proteína Pós-Traducional
13.
Biomedicines ; 8(8)2020 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-32752275

RESUMO

Mechanisms of lipid homeostasis and its impairment are of crucial importance for atherogenesis, and their understanding is necessary for successful development of new therapeutic approaches. In the arterial wall, macrophages play a prominent role in intracellular lipid accumulation, giving rise to foam cells that populate growing atherosclerotic plaques. Under normal conditions, macrophages are able to process substantial amounts of lipids and cholesterol without critical overload of the catabolic processes. However, in atherosclerosis, these pathways become inefficient, leading to imbalance in cholesterol and lipid metabolism and disruption of cellular functions. In this review, we summarize the existing knowledge on the involvement of macrophage lipid metabolism in atherosclerosis development, including both the results of recent studies and classical concepts, and provide a detailed description of these processes from the moment of lipid uptake with lipoproteins to cholesterol efflux.

14.
Life (Basel) ; 10(9)2020 Aug 22.
Artigo em Inglês | MEDLINE | ID: mdl-32842589

RESUMO

The search for markers of predisposition to atherosclerosis development is very important for early identification of individuals with a high risk of cardiovascular disease. The aim of the present study was to investigate the association of mitochondrial DNA mutations with carotid intima-media thickness and to determine the impact of mitochondrial heteroplasmy measurements in the prognosis of atherosclerosis development. This cross-sectional, population-based study was conducted in 468 subjects from the Novosibirsk region. It was shown that the mean (carotid intima-media thickness) cIMT correlated with the following mtDNA mutations: m.15059G>A (r = 0.159, p = 0.001), m.12315G>A (r = 0.119; p = 0.011), m.5178C>A (r = 0.114, p = 0.014), and m.3256C>T (r = 0.130, p = 0.011); a negative correlation with mtDNA mutations m.14846G>A (r = -0.111, p = 0.042) and m.13513G>A (r = -0.133, p = 0.004) was observed. In the linear regression analysis, the addition of the set of mtDNA mutations to the conventional cardiovascular risk factors increased the ability to predict the cIMT variability from 17 to 27%. Multi-step linear regression analysis revealed the most important predictors of mean cIMT variability: age, systolic blood pressure, blood levels of total cholesterol, LDL and triglycerides, as well as the mtDNA mutations m.13513G>A, m.15059G>A, m.12315G>A, and m.3256C>T. Thus, a high predictive value of mtDNA mutations for cIMT variability was demonstrated. The association of mutation m.13513G>A and m.14846G>A with a low value of cIMT, demonstrated in several studies, represents a potential for the development of anti-atherosclerotic gene therapy.

15.
Biomedicines ; 8(7)2020 Jul 13.
Artigo em Inglês | MEDLINE | ID: mdl-32668733

RESUMO

The endoplasmic reticulum (ER) stress is an important event in the pathogenesis of different human disorders, including atherosclerosis. ER stress leads to disturbance of cellular homeostasis, apoptosis, and in the case of macrophages, to foam cell formation and pro-inflammatory cytokines production. In atherosclerosis, several cell types can be affected by ER stress, including endothelial cells, vascular smooth muscular cells, and macrophages. Modified low-density lipoproteins (LDL) and cytokines, in turn, can provoke ER stress through different processes. The signaling cascades involved in ER stress initiation are complex and linked to other cellular processes, such as lysosomal biogenesis and functioning, autophagy, mitochondrial homeostasis, and energy production. In this review, we discuss the underlying mechanisms of ER stress formation and the interplay of lipid accumulation and pro-inflammatory response. We will specifically focus on macrophages, which are the key players in maintaining chronic inflammatory milieu in atherosclerotic lesions, and also a major source of lipid-accumulating foam cells.

16.
Biology (Basel) ; 9(6)2020 Jun 25.
Artigo em Inglês | MEDLINE | ID: mdl-32630516

RESUMO

The role of mitochondria in cardiovascular diseases is receiving ever growing attention. As a central player in the regulation of cellular metabolism and a powerful controller of cellular fate, mitochondria appear to comprise an interesting potential therapeutic target. With the development of DNA sequencing methods, mutations in mitochondrial DNA (mtDNA) became a subject of intensive study, since many directly lead to mitochondrial dysfunction, oxidative stress, deficient energy production and, as a result, cell dysfunction and death. Many mtDNA mutations were found to be associated with chronic human diseases, including cardiovascular disorders. In particular, 17 mtDNA mutations were reported to be associated with ischemic heart disease in humans. In this review, we discuss the involvement of mitochondrial dysfunction in the pathogenesis of atherosclerosis and describe the mtDNA mutations identified so far that are associated with atherosclerosis and its risk factors.

17.
Biology (Basel) ; 9(8)2020 Jul 22.
Artigo em Inglês | MEDLINE | ID: mdl-32708035

RESUMO

Desialylation-loss of terminal sialic acid residues from glycoconjugates catalyzed by sialidases-is involved in many human diseases and is considered a key molecular event of atherosclerosis onset. Desialylated low-density lipoproteins with atherogenic properties have been detected in human blood previously. However, there is currently no consensus on the origin of desialylation activity in the bloodstream. Here, we suggest viral intervention as a possible explanation. In order to address our hypothesis, we studied seasonal patterns of blood serum sialidase enzymatic activity and designed an approach to detect and quantify viral sialidase genetic presence. Increased sialidase activity in autumn-winter combined with detectable levels of influenza virus sialidase mRNA suggests exogenous viral sialidase as a viable component of desialylation in human blood, providing new insights on the molecular background of atherogenesis.

18.
Biomedicines ; 8(7)2020 Jul 07.
Artigo em Inglês | MEDLINE | ID: mdl-32645916

RESUMO

People exposed to chronic stress age rapidly. The telomeres in their cells of all types shorten faster. Inflammation is another important feature of stress that, along with aging, accounts for the phenomenon of inflammaging. In addition to aging itself, inflammaging can contribute to the development of several pathologies, including atherosclerosis, diabetes, hypertension, and others. Oxidative stress is one of the main mechanisms related to stress. Oxidative stress is caused by the over-production of reactive oxygen species (ROS) that can damage various tissues. The main source of ROS is mitochondria. Being suppressed by mitochondrial mutations, mitophagy can aggravate the situation. In this case, the aging-specific pro-inflammatory changes are amplified. It happens because of the inability of cells to maintain the normal state of mitochondria. Macrophages are the crucial element of the innate immunity associated with the chronic inflammation and, subsequently, with the inflammaging. In this review, we focus on the therapy approaches potentially reducing the deleterious effects of oxidative stress. These include stimulation of mitophagy, activation of mitochondrial uncoupling, induction of the expression of the telomerase catalytic component gene, and use of antioxidants. Any method reducing oxidative stress should improve post-traumatic stress disorder.

19.
Biomedicines ; 8(6)2020 Jun 18.
Artigo em Inglês | MEDLINE | ID: mdl-32570831

RESUMO

Atherosclerosis is a multifactorial disease of the cardiovascular system associated with aging, inflammation, and oxidative stress. An important role in the development of atherosclerosis play elevated plasma lipoproteins. A number of external factors (smoking, diabetes, infections) can also contribute to the development of the disease. For a long time, atherosclerosis remains asymptomatic, therefore, the search for early markers of the disease is critical for the timely management and better outcomes for patients. Mitochondrial dysfunction and mitochondrial DNA (mtDNA) damage appear to connect different aspects of atherosclerosis pathogenesis. To date, multiple lines of research have demonstrated the strong association of mitochondrial dysfunction with the development of various human diseases. Therapies aimed at restoring the mitochondrial function are being actively developed, and are expected to broaden the therapeutic possibilities for several chronic human diseases. The development of such therapies depends on our understanding of the functional roles of different mtDNA variants associated with one or another disorder, and the molecular mechanisms linking mitochondrial dysfunction with a given pathological feature. These questions are, however, challenging and require future intensive research. This review summarizes the recent studies and describes the central processes of the development of atherosclerosis, and shows their relationship with mitochondrial dysfunction. One of the promising therapeutic approaches for future atherosclerosis treatments is the use of mitochondria-targeted antioxidants. Future studies should focus on characterizing the mechanisms of mitochondrial involvement in cardiovascular pathologies to better direct the search for novel therapies.

20.
Front Pharmacol ; 11: 642, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32528276

RESUMO

Atherosclerosis is one of the most common diseases of the cardiovascular system that leads to the development of life-threatening conditions, such as heart attack and stroke. Arthrosclerosis affects various arteries in the human body, but is especially dangerous in the arteries alimenting heart and brain, aorta, and arteries of the lower limbs. By its pathophysiology, atherosclerosis is an inflammatory disease. During the pathological process, lesions of arterial intima in the form of focal thickening are observed, which form atherosclerotic plaques as the disease progresses further. Given the significance of atherosclerosis for the global health, the search for novel effective therapies is highly prioritized. However, despite the constant progress, our understanding of the mechanisms of atherogenesis is still incomplete. One of the remaining puzzles in atherosclerosis development is the focal distribution of atherosclerotic lesions in the arterial wall. It implies the existence of certain mosaicism within the tissue, with some areas more susceptible to disease development than others, which may prove to be important for novel therapy development. There are many hypotheses explaining this phenomenon, for example, the influence of viruses, and the spread in the endothelium of the vessel multinucleated giant endothelial cells. We suggest the local variations of the mitochondrial genome as a possible explanation of this mosaicism. In this review, we discuss the role of genetic variations in the nuclear and mitochondrial genomes that influence the development of atherosclerosis. Changes in the mitochondrial and nuclear genome have been identified as independent factors for the development of the disease, as well as potential diagnostic markers.

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