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Systemic lupus erythematosus (SLE) is a complex autoimmune disorder characterized by the presence of various serum autoantibodies and multi-system effects, predominantly affecting young female patients. The pathogenesis of SLE involves a combination of genetic factors, environmental triggers, and pathogen invasions that disrupt immune cell activation, leading to the release of autoantibodies and chronic inflammation. Mitochondria, as the primary cellular powerhouses, play a crucial role in SLE development through their control of energy generation, reactive oxygen species (ROS) production, and cellular apoptotic pathways. Dysregulation of mitochondrial structure and function can contribute to the immune dysregulation, oxidative stress, and inflammation seen in SLE. Recent research has highlighted the impact of mitochondrial dysfunction on various immune cells involved in SLE pathogenesis, such as T-lymphocytes, B-lymphocytes, neutrophils, and plasmacytoid dendritic cells. Mitochondrial dysfunction in these immune cells leads to increased ROS production, disrupted mitophagy, and alterations in energy metabolism, contributing to immune dysregulation and inflammation. Moreover, genetic variations in mitochondrial DNA (mtDNA) and abnormalities in mitochondrial dynamics have been linked to the pathogenesis of SLE, exacerbating oxidative stress and immune abnormalities. Targeting mitochondrial function has emerged as a promising therapeutic approach for SLE. Drugs such as sirolimus, N-acetylcysteine, coenzyme Q10, and metformin have shown potential in restoring mitochondrial homeostasis, reducing oxidative stress, and modulating immune responses in SLE. These agents have demonstrated efficacy in preclinical models and clinical studies by improving disease activity, reducing autoantibody titers, and ameliorating organ damage in SLE patients. In conclusion, this review underscores the critical role of mitochondria in the pathogenesis of SLE and the potential of targeting mitochondrial dysfunction as a novel therapeutic strategy for improving outcomes in SLE patients. Further investigation into the mechanisms underlying mitochondrial involvement in SLE and the development of targeted mitochondrial therapies hold promise for advancing SLE treatment and enhancing patient care.

Atherosclerosis is extremely widespread. Traditionally, it is considered a disease of older people, who most often experience problems with the heart and blood vessels. While much attention from the scientific community has been paid to studying the association between aging and atherosclerosis, as well as its consequences, there is evidence that atherosclerosis occurs at an early age. Atherosclerosis may form both during intrauterine development and in childhood. Nutrition plays an important role in childhood atherosclerosis, along with previous infectious diseases and excess weight of both the child and the mother. In the present review, we examined the development of atherosclerosis and the prerequisites in childhood.

Atherosclerosis poses a significant and widespread problem at the population level. Consequently, there is a pressing need to develop effective methods to reduce the risk associated with this condition, which holds a prominent position in cardiology research. The primary manifestation of atherosclerosis involves plaque formation on the walls of coronary arteries. These plaques not only disrupt blood flow but also raise the likelihood of thrombosis and subsequent cardiovascular events. Unfortunately, atherosclerosis itself is usually asymptomatic, resulting in challenges with diagnosis and a delayed initiation of treatment. Hence, strategies focusing on the regression of existing plaques within blood vessels play a crucial role. The present review encompasses comprehensive data on the regression of coronary atherosclerotic plaques, examining both the underlying mechanisms and a range of regression strategies, encompassing lifestyle modifications to medical interventions.

In the modern world, cardiovascular diseases have a special place among the most common causes of death. Naturally, this widespread problem cannot escape the attention of scientists and researchers. One of the main conditions preceding the development of fatal cardiovascular diseases is atherosclerosis. Despite extensive research into its pathogenesis and possible prevention and treatment strategies, many gaps remain in our understanding of this disease. For example, the concept of multiple low-density lipoprotein modifications was recently stated, in which desialylation is of special importance. Apart from this, sialic acids are known to be important contributors to processes such as endothelial dysfunction and inflammation, which in turn are major components of atherogenesis. In this review, we have collected information on sialic acid metabolism, analyzed various aspects of its implication in atherosclerosis at different stages, and provided an overview of the role of particular groups of enzymes responsible for sialic acid metabolism in the context of atherosclerosis.

The proteins of the Wnt family are involved in a variety of physiological processes by means of several canonical and noncanonical signaling pathways. Wnt signaling has been recently identified as a major player in atherogenesis. In this review, we summarize the existing knowledge on the influence of various components of the Wnt signaling pathways on the initiation and progression of atherosclerosis and associated conditions. We used the PubMed database to search for recent papers on the involvement of the Wnt pathways in atherosclerosis. We used the combination of "Wnt" and "atherosclerosis" keywords to find the initial papers, and chose papers published after 2018. In the first section of the paper, we describe the general mechanisms of the Wnt signaling pathways and their components. The next section is dedicated to existing studies assessing the implication of Wnt signaling elements in different atherogenic processes, such as cholesterol retention, endothelial dysfunction, vascular inflammation, and atherosclerotic calcification of the vessels. Lastly, various therapeutic strategies based on interference with the Wnt signaling pathways are considered. We also compare the efficacy and availability of the proposed treatment methods. Wnt signaling can be considered a potential target in the treatment and prevention of atherosclerosis. Therefore, in this review, we reviewed evidences showing that wnt signaling is an important signal for developing appropriate treatment strategies for atherosclerosis., Competing Interests: Conflict of Interest: The authors have no conflicts of interest to declare., (Copyright © 2023 The Korean Society of Lipid and Atherosclerosis.)

Cardiovascular disease is one of the main death causes globally. Effective cardiovascular risk management requires a thorough understanding of the mechanisms underlying the disorder. Establishing early markers of the disease allows a timely intervention and prevention of further atherosclerosis development. Multiple studies confirm the correlation between pregnancy disorders and cardiovascular disease in the postpartum period. Moreover, over 30% of women experience adverse pregnancy outcomes. Thus, the examination of the links between these conditions and atherosclerotic cardiovascular disease may help to identify gender-specific risk factors. In this review, we will explore the association between several adverse pregnancy outcome conditions and atherosclerosis. The current analysis is based on the data from several recent studies on the mechanisms behind gestational diabetes, hypertensive disorders of pregnancy, miscarriages, and stillbirths and their implications for the female cardiovascular system.

For several decades, atherosclerosis has attracted the attention of researchers around the world. Even being a major cause of serious cardiovascular disease and events, atherosclerosis is still not fully understood. Despite the fact that the main players in the pathogenesis of atherosclerosis are well known, many mechanisms of their implementation and interactions remain unknown. The same can be said about the risk factors for atherosclerosis. Many of them are known, but exactly how they work remains to be seen. The main objective of this review is to summarize the latest data on sex as a biological variable in atherosclerosis in humans and animals; to determine what we do not still know about how sex affects the process of growth and complications of atherosclerosis. In this review, we summarized data on sex differences at 3 atherosclerotic aspects: inflammation, vascular remodeling, and plaque morphology. With all overviewed data, we came to the conclusion on the atheroprotective role of female sex., Competing Interests: The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article., (© The Author(s) 2023.)

Atherosclerosis is a major global health problem. Being a harbinger of a large number of cardiovascular diseases, it ultimately leads to morbidity and mortality. At the same time, effective measures for the prevention and treatment of atherosclerosis have not been developed, to date. All available therapeutic options have a number of limitations. To understand the mechanisms behind the triggering and development of atherosclerosis, a deeper understanding of molecular interactions is needed. Heat shock proteins are important for the normal functioning of cells, actively helping cells adapt to gradual changes in the environment and survive in deadly conditions. Moreover, multiple HSP families play various roles in the progression of cardiovascular disorders. Some heat shock proteins have been shown to have antiatherosclerotic effects, while the role of others remains unclear. In this review, we considered certain aspects of the antiatherosclerotic activity of a number of heat shock proteins.

Atherosclerosis was and remains an extremely common and serious health problem. Since the elderly are most at risk of cardiovascular risk, and the average life expectancy is increasing, the spread of atherosclerosis and its consequences increases as well. One of the features of atherosclerosis is its asymptomaticity. This factor makes it difficult to make a timely diagnosis. This entails the lack of timely treatment and even prevention. To date, in the arsenal of physicians, there is only a limited set of methods to suspect and fully diagnose atherosclerosis. In this review, we have tried to briefly describe the most common and effective methods for diagnosing atherosclerosis., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (© 2023 Poznyak, Sukhorukov, Eremin, Nadelyaeva and Orekhov.)

It is known that lipid metabolism disorders are involved in a wide range of pathologies. These pathologies include cardiovascular, metabolic, neurodegenerative diseases, and even cancer. All these diseases lead to serious health consequences, which makes it impossible to ignore them. Unfortunately, these diseases most often have a complex pathogenesis, which makes it difficult to study them and, in particular, diagnose and treat them. HDL is an important part of lipid metabolism, performing many functions under normal conditions. One of such functions is the maintaining of the reverse cholesterol transport. These functions are also implicated in pathology development. Thus, HDL contributes to vascular protection, which has been demonstrated in various conditions: Alzheimer's disease, atherosclerosis, etc. Many studies have shown that serum levels of HDL cholesterol correlate negatively with CV risk. With these data, HDL-C is a promising therapeutic target. In this manuscript, we reviewed HDL-based therapeutic strategies that are currently being used or may be developed soon.

Since the end of the 20th century, it has been clear that atherosclerosis is an inflammatory disease. However, the main triggering mechanism of the inflammatory process in the vascular walls is still unclear. To date, many different hypotheses have been put forward to explain the causes of atherogenesis, and all of them are supported by strong evidence. Among the main causes of atherosclerosis, which underlies these hypotheses, the following can be mentioned: lipoprotein modification, oxidative transformation, shear stress, endothelial dysfunction, free radicals' action, homocysteinemia, diabetes mellitus, and decreased nitric oxide level. One of the latest hypotheses concerns the infectious nature of atherogenesis. The currently available data indicate that pathogen-associated molecular patterns from bacteria or viruses may be an etiological factor in atherosclerosis. This paper is devoted to the analysis of existing hypotheses for atherogenesis triggering, and special attention is paid to the contribution of bacterial and viral infections to the pathogenesis of atherosclerosis and cardiovascular disease.

Despite being the most common treatment strategy in the management of atherosclerosis and subsequent cardiovascular disease, classical statin therapy has certain disadvantages, including numerous side effects. In addition, a regimen with daily administration of the drug is hard to comply with. Thus, there is a need for modern and more efficient therapeutic strategies in CVD treatment. There is extensive evidence indicating that PCSK9 promotes atherogenesis through a variety of mechanisms. Thus, new treatment methods can be developed that prevent or alleviate atherosclerotic cardiovascular disease by targeting PCSK9. Comprehensive understanding of its atherogenic properties is a necessary precondition for the establishment of new therapeutic strategies. In this review, we will summarize the available data on the role of PCSK9 in the development and progression of atherosclerosis. In the last section, we will consider existing PCSK9 inhibitors.

Atherosclerosis is a complex disease, and there are many factors that influence its development and the course of the disease. A deep understanding of the pathological mechanisms underlying atherogenesis is needed to develop optimal therapeutic strategies and treatments. In this review, we have focused on low density lipoproteins. According to multiple studies, their atherogenic properties are associated with multiple modifications of lipid particles. One of these modifications is Glycation. We considered aspects related to the formation of modified particles, as well as the influence of modification on their functioning. We paid special attention to atherogenicity and the role of glycated low-density lipoprotein (LDL) in atherosclerosis., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Poznyak, Sukhorukov, Surkova, Orekhov and Orekhov.)

Bacterial extracellular membrane nanovesicles (EMNs) are attracting the attention of scientists more and more every year. These formations are involved in the pathogenesis of numerous diseases, among which, of course, the leading role is occupied by infectious diseases, the causative agents of which are a range of Gram-positive and Gram-negative bacteria. A separate field for the study of the role of EMN is cancer. Extracellular membrane nanovesicles nowadays have a practical application as vaccine carriers for immunization against many infectious diseases. At present, the most essential point is their role in stimulating immune response to bacterial infections and tumor cells. The possibility of nanovesicles' practical use in several disease treatments is being evaluated. In our review, we listed diseases, focusing on their multitude and diversity, for which EMNs are essential, and also considered in detail the possibilities of using EMNs in the therapy and prevention of various pathologies.

Lipid metabolism alterations are an important component of the pathogenesis of atherosclerosis. However, it is now clear that the atherogenesis process involves more than one mechanism, and more than one condition can predispose this condition. Multiple risk factors contribute to the atherosclerosis initiation and define its course. Familial hypercholesterolaemia is a disorder of lipid metabolism that often leads to atherosclerosis development. As is clear from the disease name, the hallmark is the increased levels of low-density lipoprotein cholesterol (LDL-C) in blood. This creates favourable conditions for atherogenesis. In this review, we briefly described the familial hypercholesterolaemia and summarized data on the relationship between familial hypercholesterolaemia and atherosclerosis.

Cardiovascular diseases remain the leading cause of death and disability. The development of cardiovascular diseases is traditionally associated with various risk factors, most of which are somehow related to an unhealthy lifestyle (smoking, obesity, lack of physical activity, etc.). There are also risk factors associated with genetic predisposition, as well as the presence of concomitant diseases, especially chronic ones. One of the most striking examples is, of course, type 2 diabetes. This metabolic disorder is associated with impaired carbohydrate metabolism. The main clinical manifestation of type 2 diabetes is elevated blood glucose levels. The link between diabetes and CVD is well known, so it is logical to assume that elevated glucose levels may be important, to some extent, in the context of heart and vascular disease. In this review, we tried to summarize data on the possible role of blood glucose as a risk factor for the development of CVD.

Atherosclerosis is the major cause of cardiovascular disease, leading to a high mortality rate worldwide. Several risk factors are known to favor atherogenesis, among which are high blood pressure, smoking, diabetes mellitus, and others. Chronic kidney disease is another serious health problem associated with significant health care costs, morbidity, and mortality. Chronic kidney disease shares several risk factors with atherosclerosis and cardiovascular diseases, such as hypertension and diabetes mellitus. Additional risk factors for cardiovascular disease development should be considered in patients with chronic kidney disease. Interestingly, patients suffering from chronic kidney disease are more prone to cardiovascular problems than the general population. Moreover, chronic kidney disease is characterized by an increased atherosclerotic burden from the very early stages. The purpose of this review was to summarize data on atherosclerosis in chronic kidney disease, highlighting the specific features of the disease combination.

Atherosclerosis is a common cause of cardiovascular disease, which, in turn, is often fatal. Today, we know a lot about the pathogenesis of atherosclerosis. However, the main knowledge is that the disease is extremely complicated. The development of atherosclerosis is associated with more than one molecular mechanism, each making a significant contribution. These mechanisms include endothelial dysfunction, inflammation, mitochondrial dysfunction, oxidative stress, and lipid metabolism disorders. This complexity inevitably leads to difficulties in treatment and prevention. One of the possible therapeutic options for atherosclerosis and its consequences may be metformin, which has already proven itself in the treatment of diabetes. Both diabetes and atherosclerosis are complex metabolic diseases, the pathogenesis of which involves many different mechanisms, including those common to both diseases. This makes metformin a suitable candidate for investigating its efficacy in cardiovascular disease. In this review, we highlight aspects such as the mechanisms of action and targets of metformin, in addition to summarizing the available data from clinical trials on the effective reduction of cardiovascular risks.

Atherosclerosis is a predecessor of numerous cardiovascular diseases (CVD), which often lead to morbidity and mortality. Despite the knowledge of the pathogenesis of atherosclerosis, an essential gap in our understanding is the exact trigger mechanism. A wide range of risk factors have been discovered; however, a majority of them are too general to clarify the launching mechanism of atherogenesis. Some risk factors are permanent (age, gender, genetic heritage) and others can be modified [tobacco smoking, physical inactivity, poor nutrition, high blood pressure, type 2 diabetes (T2D), dyslipidemia, and obesity]. All of them have to be taken into account. In the scope of this review, our attention is focused on hypertension, which is considered the most widespread among all modifiable risk factors for atherosclerosis development. Moreover, high blood pressure is the most investigated risk factor. The purpose of this review is to summarize the data on hypertension as a risk factor for atherosclerosis development and the risk assessment., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The reviewer AM declared a shared affiliation with the authors EB and AG to the handling editor at the time of review., (Copyright © 2022 Poznyak, Sadykhov, Kartuesov, Borisov, Melnichenko, Grechko and Orekhov.)

Aging is one of the most intriguing processes of human ontogenesis. It is associated with the development of a wide variety of diseases affecting all organs and their systems. The victory over aging is the most desired goal of scientists; however, it is hardly achievable in the foreseeable future due to the complexity and ambiguity of the process itself. All body systems age, lose their performance, and structural disorders accumulate. The cardiovascular system is no exception. And it is cardiovascular diseases that occupy a leading position as a cause of death, especially among the elderly. The aging of the cardiovascular system is well described from a mechanical point of view. Moreover, it is known that at the cellular level, a huge number of mechanisms are involved in this process, from mitochondrial dysfunction to inflammation. It is on these mechanisms, as well as the potential for taking control of the aging of the cardiovascular system, that we focused on in this review.

It is known that the development of foci of chronic inflammation usually accompanies body aging. In these foci, senescent cells appear with a pro-inflammatory phenotype that helps maintain inflammation. Their removal with the help of senolytics significantly improves the general condition of the body and, according to many indicators, contributes to rejuvenation. The cells of the immune system participate in the initiation, development, and resolution of inflammation. With age, the human body accumulates mutations, including the cells of the bone marrow, giving rise to the cells of the immune system. We assume that a number of such mutations formed with age can lead to the appearance of "naive" cells with an initially pro-inflammatory phenotype, the migration of which to preexisting foci of inflammation contributes not to the resolution of inflammation but its chronicity. One of such cell variants are monocytes carrying mitochondrial mutations, which may be responsible for comorbidity and deterioration in the prognosis of the course of pathologies associated with aging, such as atherosclerosis, arthritis, osteoporosis, and neurodegenerative diseases.

Cardiovascular disease has been, and remains, one of the leading causes of death in the modern world. The elderly are a particularly vulnerable group. The aging of the body is inevitably accompanied by the aging of all its systems, and the cardiovascular system is no exception. The aging of the cardiovascular system is a significant risk factor for the development of various diseases and pathologies, from atherosclerosis to ischemic stroke. Mitochondria, being the main supplier of energy necessary for the normal functioning of cells, play an important role in the proper functioning of the cardiovascular system. The functioning of each individual cell and the organism as a whole depends on their number, structure, and performance, as well as the correct operation of the system in removing non-functional mitochondria. In this review, we examine the role of mitochondria in the aging of the cardiovascular system, as well as in diseases (for example, atherosclerosis and ischemic stroke). We pay special attention to changes in mitochondrial dynamics since the shift in the balance between fission and fusion is one of the main factors associated with various cardiovascular pathologies.

For the past several decades, humanity has been dealing with HIV. This disease is one of the biggest global health problems. Fortunately, modern antiretroviral therapy allows patients to manage the disease, improving their quality of life and their life expectancy. In addition, the use of these drugs makes it possible to reduce the risk of transmission of the virus to almost zero. Atherosclerosis is another serious pathology that leads to severe health problems, including disability and, often, the death of the patient. An effective treatment for atherosclerosis has not yet been developed. Both types of immune response, innate and adaptive, are important components of the pathogenesis of this disease. In this regard, the peculiarities of the development of atherosclerosis in HIV carriers are of particular scientific interest. In this review, we have tried to summarize the data on atherosclerosis and its development in HIV carriers. We also looked at the classic therapeutic methods and their features concerning the concomitant diagnosis.

Atherosclerosis has been known in medicine for several centuries. As early as 1755, the Swedish anatomist Albrecht von Haller used the term "atheroma" to describe vascular lesions. Atherosclerosis may originate from an unbalanced diet or bad habits, and is mainly found in developed countries. Clinical trials have been conducted to establish the causes of atherosclerosis, and also to develop treatments for this disease. However, prevention of the disease has always been better than treatment, so vaccination may be the key to saving thousands of lives. The creation of a vaccine may be directly related to the study of autoimmune processes occurring in the body, immunity. This review considers the issues related to the involvement of the immune response in the development of atherosclerotic lesions. Modern concepts of atherogenesis, immune inflammation in atherosclerosis, and potential vaccine targets are also discussed. There is a particular focus on experimental and clinical data supporting the development of immune therapies to reduce cardiovascular risk.

Atherosclerosis is the cause of the development of serious cardiovascular disorders, leading to disability and death. Numerous processes are involved in the pathogenesis of atherosclerosis, including inflammation, endothelial dysfunction, oxidative stress, and lipid metabolism disorders. Reverse transport of cholesterol is a mechanism presumably underlying the atheroprotective effect of high-density lipoprotein. In this review, we examined disorders of cholesterol metabolism and their possible effect on atherogenesis. We paid special attention to the reverse transport of cholesterol. Transformed cholesterol metabolism results in dyslipidemia and early atherosclerosis. Reverse cholesterol transport is an endogenous mechanism by which cells export cholesterol and maintain homeostasis. It is known that one of the main factors leading to the formation of atherosclerotic plaques on the walls of blood vessels are multiple modifications of low-density lipoprotein, and the formation of foam cells following them.

For more than a decade, atherosclerosis has been one of the leading causes of death in developed countries. The issue of treatment and prevention of the disease is especially acute. Despite the huge amount of basic and clinical research, a significant number of gaps remain in our understanding of the pathogenesis of atherosclerosis, and only their closure will bring us closer to understanding the causes of the disease at the cellular and molecular levels and, accordingly, to the development of an effective treatment. One of the seemingly well-studied elements of atherogenesis is the mTOR signaling pathway. However, more and more new details are still being clarified. Therapeutic strategies associated with rapamycin have worked well in a number of different diseases, and there is every reason to believe that targeting components of the mTOR pathway may pay off in atherosclerosis as well.

Atherosclerosis is still one of the main causes of death around the globe. This condition leads to various life-threatening cardiovascular complications. However, no effective preventive measures are known apart from lifestyle corrections, and no cure has been developed. Despite numerous studies in the field of atherogenesis, there are still huge gaps in already poor understanding of mechanisms that underlie the disease. Inflammation and lipid metabolism violations are undoubtedly the key players, but many other factors, such as oxidative stress, endothelial dysfunction, contribute to the pathogenesis of atherosclerosis. This overview is focusing on the role of macrophages in atherogenesis, which are at the same time a part of the inflammatory response, and also tightly linked to the foam cell formation, thus taking part in both crucial for atherogenesis processes. Being essentially involved in atherosclerosis development, macrophages and foam cells have attracted attention as a promising target for therapeutic approaches.

Atherosclerosis is the major cause of the development of cardiovascular disease, which, in turn, is one of the leading causes of mortality worldwide. From the point of view of pathogenesis, atherosclerosis is an extremely complex disease. A huge variety of processes, such as violation of mitophagy, oxidative stress, damage to the endothelium, and others, are involved in atherogenesis; however, the main components of atherogenesis are considered to be inflammation and alterations of lipid metabolism. In this review, we want to focus on inflammation, and more specifically on the cellular elements of adaptive immunity, T and B cells. It is known that various T cells are widely represented directly in atherosclerotic plaques, while B cells can be found, for example, in the adventitia layer. Of course, such widespread and well-studied cells have attracted attention as potential therapeutic targets for the treatment of atherosclerosis. Various approaches have been developed and tested for their efficacy.

Atherosclerosis is a well-known global health problem. Despite the high prevalence of the disease, numerous aspects of pathogenesis remain unclear. Subsequently, there are still no cure or adequate preventive measures available. Atherogenesis is now considered a complex interplay between lipid metabolism alterations, oxidative stress, and inflammation. Inflammation in atherogenesis involves cellular elements of both innate (such as macrophages and monocytes) and adaptive immunity (such as B-cells and T-cells), as well as various cytokines cascades. Because inflammation is, in general, a well-investigated therapeutic target, and strategies for controlling inflammation have been successfully used to combat a number of other diseases, inflammation seems to be the preferred target for the treatment of atherosclerosis as well. In this review, we summarized data on targeting the most studied inflammatory molecular targets, CRP, IL-1β, IL-6, IFN-γ, and TNF-α. Studies in animal models have shown the efficacy of anti-inflammatory therapy, while clinical studies revealed the incompetence of existing data, which blocks the development of an effective atheroprotective drug. However, all data on cytokine targeting give evidence that anti-inflammatory therapy can be a part of a complex treatment.

Atherosclerosis has complex pathogenesis, which involves at least three serious aspects: inflammation, lipid metabolism alterations, and endothelial injury. There are no effective treatment options, as well as preventive measures for atherosclerosis. However, this disease has various severe complications, the most severe of which is cardiovascular disease (CVD). It is important to note, that CVD is among the leading causes of death worldwide. The renin-angiotensin-aldosterone system (RAAS) is an important part of inflammatory response regulation. This system contributes to the recruitment of inflammatory cells to the injured site and stimulates the production of various cytokines, such as IL-6, TNF-a, and COX-2. There is also an association between RAAS and oxidative stress, which is also an important player in atherogenesis. Angiotensin-II induces plaque formation at early stages, and this is one of the most crucial impacts on atherogenesis from the RAAS. Importantly, while stimulating the production of ROS, Angiotensin-II at the same time decreases the generation of NO. The endothelium is known as a major contributor to vascular function. Oxidative stress is the main trigger of endothelial dysfunction, and, once again, links RAAS to the pathogenesis of atherosclerosis. All these implications of RAAS in atherogenesis lead to an explicable conclusion that elements of RAAS can be promising targets for atherosclerosis treatment. In this review, we also summarize the data on treatment approaches involving cytokine targeting in CVD, which can contribute to a better understanding of atherogenesis and even its prevention.

COVID-19 is a highly contagious new infection caused by the single-stranded RNA Sars-CoV-2 virus. For the first time, this infection was recorded in December 2019 in the Chinese province of Wuhan. The virus presumably crossed the interspecies barrier and passed to humans from a bat. Initially, the disease was considered exclusively in the context of damage to the respiratory system, but it quickly became clear that the disease also entails serious consequences from various systems, including the cardiovascular system. Among these consequences are myocarditis, myocardial damage, subsequent heart failure, myocardial infarction, and Takotsubo syndrome. On the other hand, clinical data indicate that the presence of chronic diseases in a patient aggravates the course and outcome of coronavirus infection. In this context, the relationship between COVID-19 and atherosclerosis, a condition preceding cardiovascular disease and other disorders of the heart and blood vessels, is particularly interesting. The renin-angiotensin system is essential for the pathogenesis of both coronavirus disease and atherosclerosis. In particular, it has been shown that ACE2, an angiotensin-converting enzyme 2, plays a key role in Sars-CoV-2 infection due to its receptor activity. It is noteworthy that this enzyme is important for the normal functioning of the cardiovascular system. Disruptions in its production and functioning can lead to various disorders, including atherosclerosis.

Cardiovascular disease (CVD) is one of the greatest health problems affecting people worldwide. Atherosclerosis, in turn, is one of the most common causes of cardiovascular disease. Due to the high mortality rate from cardiovascular diseases, prevention and treatment at the earliest stages become especially important. This requires developing a deep understanding of the mechanisms underlying the development of atherosclerosis. It is well-known that atherogenesis is a complex multi-component process that includes lipid metabolism disorders, inflammation, oxidative stress, autophagy disorders and mitochondrial dysfunction. Autophagy is a cellular control mechanism that is critical to maintaining health and survival. One of the specific forms of autophagy is mitophagy, which aims to control and remove defective mitochondria from the cell. Particularly defective mitophagy has been shown to be associated with atherogenesis. In this review, we consider the role of autophagy, focusing on a special type of it-mitophagy-in the context of its role in the development of atherosclerosis.

It is known that the shortening of the telomeres leads to cell senescence, accompanied by acquiring of pro-inflammatory phenotype. The expression of telomerase can elongate telomeres and resist the onset of senescence. The initiation of atherosclerosis is believed to be associated with local senescence of the endothelial cells of the arteries in places with either low or multidirectional oscillatory wall shear stress. The process of regeneration of the artery surface that has begun does not lead to success for several reasons. Atherosclerotic plaques are formed, which, when developed, lead to fatal consequences, which are the leading causes of death in the modern world. The pronounced age dependence of the manifestations of atherosclerosis pushes scientists to try to link the development of atherosclerosis with telomere length. The study of the role of telomere shortening in atherosclerosis is mainly limited to measuring the telomeres of blood cells, and only in rare cases (surgery or post-mortem examination) are the telomeres of local cells available for measurement. The review discusses the basic issues of cellular aging and the interpretation of telomere measurement data in atherosclerosis, as well as the prospects for the prevention and possible treatment of atherosclerosis.

Cardiovascular pathologies maintain the leading position in mortality worldwide. Atherosclerosis is a chronic disease that can result in a variety of serious complications, such as myocardial infarction, stroke, and cardiovascular disease. Inflammation and lipid metabolism alterations play a crucial role in atherogenesis, but the details of relationships and causality of these fundamental processes remain not clear. The oxidation of LDL was considered the main atherogenic modification of LDL within the vascular wall for decades. However, recent investigations provided a growing body of evidence in support of the multiple LDL modification theory. It suggests that LDL particles undergo numerous modifications that change their size, density, and chemical properties within the blood flow and vascular wall. Oxidation is the last stage in this cascade resulting in the atherogenic properties. Moreover, recent investigations have discovered that oxLDL may have both anti-inflammatory and pro-inflammatory properties. Oxidized LDL can trigger inflammation through the activation of macrophages and other cells. After all, oxidized LDL is still a promising object for further investigations that have the potential to clarify the unknown parts of the atherogenic process. In this review, we discuss the role of oxLDL in atherosclerosis development on different levels., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Poznyak, Nikiforov, Markin, Kashirskikh, Myasoedova, Gerasimova and Orekhov.)

Background: The aim of the elucidation of mechanisms implicated in the chronification of inflammation is to shed light on the pathogenesis of disorders that are responsible for the majority of the incidences of diseases and deaths, and also causes of ageing. Atherosclerosis is an example of the most significant inflammatory pathology. The inflammatory response of innate immunity is implicated in the development of atherosclerosis arising locally or focally. Modified low-density lipoprotein (LDL) was regarded as the trigger for this response. No atherosclerotic changes in the arterial wall occur due to the quick decrease in inflammation rate. Nonetheless, the atherosclerotic lesion formation can be a result of the chronification of local inflammation, which, in turn, is caused by alteration of the response of innate immunity., Objective: In this review, we discussed potential mechanisms of the altered response of the immunity in atherosclerosis with a particular emphasis on mitochondrial dysfunctions., Conclusion: A few mitochondrial dysfunctions can be caused by the mitochondrial DNA (mtDNA) mutations. Moreover, mtDNA mutations were found to affect the development of defective mitophagy. Modern investigations have demonstrated the controlling mitophagy function in response to the immune system. Therefore, we hypothesized that impaired mitophagy, as a consequence of mutations in mtDNA, can raise a disturbed innate immunity response, resulting in the chronification of inflammation in atherosclerosis., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Atherosclerosis is a major cause of disease-related mortality around the globe. The main characteristic of the disease is an accumulation of plaque on the arterial wall and subsequent erosion or rupture of some plaques. Atherosclerosis often leads to cardiovascular disease and such acute complications as myocardial infarction or ischemic stroke due to thrombus formation. Most recent advances in atherosclerotic research state that the modifications of low-density lipoprotein (LDL) are one of the most significant stages in the disease initiation, and among these modifications desialylation is of particular interest. Sialic acids are widely expressed on all types of cells of many organisms and participate in numerous biological processes. Regarding atherosclerosis, sialidases that are responsible for the regulation of the sialic component of different molecules, are probably one of the most crucial enzymatic families. Sufficient sialylation of vascular endothelium defines its susceptibility to an atherogenic plaque formation. Moreover, the desialylation of LDL provokes an accumulation of cholesterol and lipids in the arterial walls. According to the multiple involvements of sialic acids and related enzymes, sialidases, in the initiation and development of atherosclerosis, the deeper understanding of their exact role, as well as cellular and molecular mechanisms, will allow creating more targeted and effective therapeutic and diagnostic approaches.

The current view on atherosclerosis positions it as a multifactorial disorder that results from the interplay between lipid metabolism disturbances and inflammatory processes. Oxidative stress is proven to be one of the initiating factors in atherosclerosis development, being implicated both in the inflammatory response and in atherogenic modifications of lipoproteins that facilitate lipid accumulation in the arterial wall. The hallmark of oxidative stress is the elevated level of reactive oxygen species (ROS). Correspondingly, the activity of major ROS-generating enzymes, including nicotinamide adenine dinucleotide phosphate (NADPH) oxidases, xanthine oxidases, and cyclooxygenases, is an important element in atherosclerosis development. In particular, the role of NADPH oxidases in atherosclerosis development has become a subject of intensive research. Aberrant activity of NADPH oxidases was shown to be associated with cardiovascular disease in humans. With regard to atherosclerosis, several important pathological components of the disease development, including endothelial dysfunction, inflammation, and vascular remodeling, involve aberrations in NADPH oxidases functioning. In humans, NADPH oxidases are represented by four isoforms expressed in vascular tissues, where they serve as the main source of ROS during atherogenesis. Moreover, recent studies have demonstrated their impact on vascular remodeling processes. Interestingly, one of the NADPH oxidase isoforms, NOX4, was shown to have an atheroprotective effect. Despite the growing evidence of the crucial involvement of NADPH oxidases in atherosclerosis pathogenesis, the available data still remains controversial. In this narrative review, we summarize the current knowledge of the role of NADPH oxidases in atherosclerosis and outline the future directions of research.

Atherosclerosis is a serious disorder, with numerous potential complications such as cardiovascular disease, ischemic stroke, and myocardial infarction. The origin of atherosclerosis is related to chronic inflammation, lipid metabolism alterations, and oxidative stress. Inflammasomes are the cytoplasmic multiprotein complex triggering the activation of inflammatory response. NLRP3 inflammasomes have a specific activation pathway that involves numerous stimuli, including a wide range of PAMPs and DAMPs. Recent studies of atherosclerotic pathology are focused on the mitochondria that appear to be a promising target for therapeutic approach development. Mitochondria are the main source of reactive oxygen species (ROS) associated with oxidative stress. It was previously shown that NLRP3 inflammasome activation results in mitochondrial damage, but the exact mechanisms of this need to be specified. In this review, we focused on the features of NLRP3 inflammasomes and their significance for atherosclerosis, especially concerning mitochondria., Competing Interests: The authors declare no conflict of interest

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.

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.

Non-contagious diseases such as atherosclerosis, diabetes, cardiovascular disease, cancer, chronic respiratory diseases, and mental disorders hold responsibility for major health losses worldwide. Atherosclerosis was found to be the leading cause of deaths due to the major consequences, such as cardiovascular disease, stroke, ischemic heart disease, myocardial infarction, and others. The number of patients with atherosclerosis increases with every passing year. If treatment is not started on time, every second patient dies within 10 years. Moreover, the disease leads to persistent disability of patients, most of whom are of active working age. Atherosclerosis is a metabolic disorder characterized by hyperlipidemia and chronic inflammation. Although this disease annually kills a huge number of people, patients are now offered various therapeutic techniques, however, with different efficiencies. The scientific community is working to develop more effective means for treatment and precaution of the disease, regardless of the difficulties in understanding the causes of the health problem and the characteristics of its course. There are numerous strategies in the treatment and prevention of atherosclerosis, focusing on different aspects of the disease, such as inflammation, lipid metabolism alterations, or others, but none of them, unfortunately, is absolutely effective. In this review, we focused on the treatment approaches aimed at remedy the disruptions of lipid metabolism that are currently used in clinical practice., Competing Interests: None., (AJCD Copyright © 2020.)

Accumulation of lipid-laden (foam) cells in the arterial wall is known to be the earliest step in the pathogenesis of atherosclerosis. There is almost no doubt that atherogenic modified low-density lipoproteins (LDL) are the main sources of accumulating lipids in foam cells. Atherogenic modified LDL are taken up by arterial cells, such as macrophages, pericytes, and smooth muscle cells in an unregulated manner bypassing the LDL receptor. The present study was conducted to reveal possible common mechanisms in the interaction of macrophages with associates of modified LDL and non-lipid latex particles of a similar size. To determine regulatory pathways that are potentially responsible for cholesterol accumulation in human macrophages after the exposure to naturally occurring atherogenic or artificially modified LDL, we used transcriptome analysis. Previous studies of our group demonstrated that any type of LDL modification facilitates the self-association of lipoprotein particles. The size of such self-associates hinders their interaction with a specific LDL receptor. As a result, self-associates are taken up by nonspecific phagocytosis bypassing the LDL receptor. That is why we used latex beads as a stimulator of macrophage phagocytotic activity. We revealed at least 12 signaling pathways that were regulated by the interaction of macrophages with the multiple-modified atherogenic naturally occurring LDL and with latex beads in a similar manner. Therefore, modified LDL was shown to stimulate phagocytosis through the upregulation of certain genes. We have identified at least three genes ( F2RL1 , EIF2AK3 , and IL15 ) encoding inflammatory molecules and associated with signaling pathways that were upregulated in response to the interaction of modified LDL with macrophages. Knockdown of two of these genes, EIF2AK3 and IL15 , completely suppressed cholesterol accumulation in macrophages. Correspondingly, the upregulation of EIF2AK3 and IL15 promoted cholesterol accumulation. These data confirmed our hypothesis of the following chain of events in atherosclerosis: LDL particles undergo atherogenic modification; this is accompanied by the formation of self-associates; large LDL associates stimulate phagocytosis; as a result of phagocytosis stimulation, pro-inflammatory molecules are secreted; these molecules cause or at least contribute to the accumulation of intracellular cholesterol. This chain of events may explain the relationship between cholesterol accumulation and inflammation. The primary sequence of events in this chain is related to inflammatory response rather than cholesterol accumulation.

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., (© 2020 The Authors. Pharmacology Research & Perspectives published by John Wiley & Sons Ltd, British Pharmacological Society and American Society for Pharmacology and Experimental Therapeutics.)

Atherosclerosis can be regarded as chronic inflammatory disease affecting the arterial wall. Despite the recent progress in studying the pathogenesis of atherosclerosis, some of the pathogenic mechanisms remain to be fully understood. Among these mechanisms is oxidative stress, which is closely linked to foam cells formation and other key events in atherosclerosis development. Two groups of enzymes are involved in the emergence of oxidative stress: Pro-oxidant (including NADPH oxidases, xanthine oxidases, and endothelial nitric oxide synthase) and antioxidant (such as superoxide dismutase, catalases, and thioredoxins). Pro-oxidant enzymes in normal conditions produce moderate concentrations of reactive oxidant species that play an important role in cell functioning and can be fully utilized by antioxidant enzymes. Under pathological conditions, activities of both pro-oxidant and antioxidant enzymes can be modified by numerous factors that can be relevant for developing novel therapies. Recent studies have explored potential therapeutic properties of antioxidant molecules that are capable to eliminate oxidative damage. However, the results of these studies remain controversial. Other perspective approach is to inhibit the activity of pro-oxidant enzymes and thus to slow down the progression of atherosclerosis. In this review we summarized the current knowledge on oxidative stress in atherosclerosis and potential antioxidant approaches. We discuss several important antioxidant molecules of plant origin that appear to be promising for treatment of atherosclerosis.

Atherosclerosis is a multifactorial chronic disease that affects large arteries and may lead to fatal consequences. According to current understanding, inflammation and lipid accumulation are the two key mechanisms of atherosclerosis development. Animal models based on genetically modified mice have been developed to investigate these aspects. One such model is low-density lipoprotein (LDL) receptor knockout (KO) mice ( ldlr -/- ), which are characterized by a moderate increase of plasma LDL cholesterol levels. Another widely used genetically modified mouse strain is apolipoprotein-E KO mice ( apoE -/- ) that lacks the primary lipoprotein required for the uptake of lipoproteins through the hepatic receptors, leading to even greater plasma cholesterol increase than in ldlr -/- mice. These and other animal models allowed for conducting genetic studies, such as genome-wide association studies, microarrays, and genotyping methods, which helped identifying more than 100 mutations that contribute to atherosclerosis development. However, translation of the results obtained in animal models for human situations was slow and challenging. At the same time, genetic studies conducted in humans were limited by low sample sizes and high heterogeneity in predictive subclinical phenotypes. In this review, we summarize the current knowledge on the use of KO mice for identification of genes implicated in atherosclerosis and provide a list of genes involved in atherosclerosis-associated inflammatory pathways and their brief characteristics. Moreover, we discuss the approaches for candidate gene search in animals and humans and discuss the progress made in the field of epigenetic studies that appear to be promising for identification of novel biomarkers and therapeutic targets.

Atherosclerosis is associated with acute cardiovascular conditions, such as ischemic heart disease, myocardial infarction, and stroke, and is the leading cause of morbidity and mortality worldwide. Our understanding of atherosclerosis and the processes triggering its initiation is constantly improving, and, during the last few decades, many pathological processes related to this disease have been investigated in detail. For example, atherosclerosis has been considered to be a chronic inflammation triggered by the injury of the arterial wall. However, recent works showed that atherogenesis is a more complex process involving not only the immune system, but also resident cells of the vessel wall, genetic factors, altered hemodynamics, and changes in lipid metabolism. In this review, we focus on foam cells that are crucial for atherosclerosis lesion formation. It has been demonstrated that the formation of foam cells is induced by modified low-density lipoprotein (LDL). The beneficial effects of the majority of therapeutic strategies with generalized action, such as the use of anti-inflammatory drugs or antioxidants, were not confirmed by clinical studies. However, the experimental therapies targeting certain stages of atherosclerosis, among which are lipid accumulation, were shown to be more effective. This emphasizes the relevance of future detailed investigation of atherogenesis and the importance of new therapies development., Competing Interests: The authors declare no conflict of interest.

Background: Atherosclerosis is a chronic inflammatory condition that affects different arteries in the human body and often leads to severe neurological complications, such as stroke and its sequelae. Affected blood vessels develop atherosclerotic lesions in the form of focal thickening of the intimal layer, so called atherosclerotic plaques., Objectives: Despite the high priority of atherosclerosis research for global health and the numerous preclinical and clinical studies conducted, currently, there is no effective pharmacological treatment that directly impacts atherosclerotic plaques. Many knowledge gaps exist in our understanding of the mechanisms of plaque formation. In this review, we discuss the role of mitochondria in different cell types involved in atherogenesis and provide information about mtDNA mutations associated with the disease., Results: Mitochondria of blood and arterial wall cells appear to be one of the important factors in disease initiation and development. Significant experimental evidence connects oxidative stress associated with mitochondrial dysfunction and vascular disease. Moreover, mitochondrial DNA (mtDNA) deletions and mutations are being considered as potential disease markers. Further study of mtDNA damage and associated dysfunction may open new perspectives for atherosclerosis treatment., Conclusion: Mitochondria can be considered as important disease-modifying factors in several chronic pathologies. Deletions and mutations of mtDNA may be used as potential disease markers. Mitochondria-targeting antioxidant therapies appear to be promising for the development of treatment of atherosclerosis and other diseases associated with oxidative stress and chronic inflammation., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Atherosclerosis retains the leading position among the causes of global morbidity and mortality worldwide, especially in the industrialized countries. Despite the continuing efforts to investigate disease pathogenesis and find the potential points of effective therapeutic intervention, our understanding of atherosclerosis mechanisms remains limited. This is partly due to the multifactorial nature of the disease pathogenesis, when several factors so different as altered lipid metabolism, increased oxidative stress, and chronic inflammation act together leading to the formation and progression of atherosclerotic plaques. Adequate animal models are currently indispensable for studying these processes and searching for novel therapies. Animal models based on rodents, such as mice and rats, and rabbits represent important tools for studying atherosclerosis. Currently, genetically modified animals allow for previously unknown possibilities in modelling the disease and its most relevant aspects. In this review, we describe the recent progress made in creating such models and discuss the most important findings obtained with them to date.