Role of Lipid Accumulation and Inflammation in Atherosclerosis: Focus on Molecular and Cellular Mechanisms

Atherosclerosis is a chronic lipid-driven and maladaptive inflammatory disease of arterial intima. It is characterized by the dysfunction of lipid homeostasis and signaling pathways that control the inflammation. This article reviews the role of inflammation and lipid accumulation, especially low-density lipoprotein (LDL), in the pathogenesis of atherosclerosis, with more emphasis on cellular mechanisms. Furthermore, this review will briefly highlight the role of medicinal plants, long non-coding RNA (lncRNA), and microRNAs in the pathophysiology, treatment, and prevention of atherosclerosis. Lipid homeostasis at various levels, including receptor-mediated uptake, synthesis, storage, metabolism, efflux, and its impairments are important for the development of atherosclerosis. The major source of cholesterol and lipid accumulation in the arterial wall is proatherogenic modified low-density lipoprotein (mLDL). Modified lipoproteins, such as oxidized low-density lipoprotein (ox-LDL) and LDL binding with proteoglycans of the extracellular matrix in the intima of blood vessels, cause aggregation of lipoprotein particles, endothelial damage, leukocyte recruitment, foam cell formation, and inflammation. Inflammation is the key contributor to atherosclerosis and participates in all phases of atherosclerosis. Also, several studies have shown that microRNAs and lncRNAs have appeared as key regulators of several physiological and pathophysiological processes in atherosclerosis, including regulation of HDL biogenesis, cholesterol efflux, lipid metabolism, regulating of smooth muscle proliferation, and controlling of inflammation. Thus, both lipid homeostasis and the inflammatory immune response are closely linked, and their cellular and molecular pathways interact with each other.</p

Ace2 is an adjacent element of atherosclerosis and covid-19 pathogenesis

COVID-19 is a highly contagious new infection caused by the single-stranded RNA SarsCoV-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.Funding: This work was supported by the Russian Science Foundation (grant number 18-15-00254).Scopu

Mitochondrial dysfunction and chronic inflammation in polycystic ovary syndrome

Polycystic ovarian syndrome (PCOS) is the most common endocrine–metabolic disorder affecting a vast population worldwide; it is linked with anovulation, mitochondrial dysfunctions and hormonal disbalance. Mutations in mtDNA have been identified in PCOS patients and likely play an important role in PCOS aetiology and pathogenesis; however, their causative role in PCOS development requires further investigation. As a low-grade chronic inflammation disease, PCOS patients have permanently elevated levels of inflammatory markers (TNF-α, CRP, IL-6, IL-8, IL-18). In this review, we summarise recent data regarding the role of mtDNA mutations and mitochondrial malfunctions in PCOS pathogenesis. Furthermore, we discuss recent papers dedicated to the identification of novel biomarkers for early PCOS diagnosis. Finally, traditional and new mitochondria-targeted treatments are discussed. This review intends to emphasise the key role of oxidative stress and chronic inflammation in PCOS pathogenesis; however, the exact molecular mechanism is mostly unknown and requires further investigation.Funding: This work was supported by the Russian Science Foundation (Grant #20-15-00337).Scopu

Macrophages in Health and Non-Infectious Disease 2.0

This Special Issue (SI) has collected the most recent publications on the mechanisms that macrophages use to regulate homeostasis and their involvement in the pathogenesis of various non-infectious diseases [...

Macrophages in Health and Non-Infectious Disease

In this Special Issue of Biomedicines, we have many insightful reviews and research papers on the subject “Macrophages in Health and Non-infectious Disease”, but first; we should discuss briefly the current situation in the field [...

Lipids and Lipoproteins in Health and Disease

This Special Issue, &ldquo;Lipids and Lipoproteins in Health and Disease: Focus on Targeting Atherosclerosis&rdquo;, contains research articles and reviews devoted to the study of lipids in different processes, with a focus on the pathological changes that happen during atherosclerosis [...

Thirty-Five-Year History of Desialylated Lipoproteins Discovered by Vladimir Tertov

Atherosclerosis is one of the leading causes of death in developed and developing countries. The atherogenicity phenomenon cannot be separated from the role of modified low-density lipoproteins (LDL) in atherosclerosis development. Among the multiple modifications of LDL, desialylation deserves to be discussed separately, since its atherogenic effects and contribution to atherogenicity are often underestimated or, simply, forgotten. Vladimir Tertov is linked to the origin of the research related to desialylated lipoproteins, including the association of modified LDL with atherogenicity, autoimmune nature of atherosclerosis, and discovery of sialidase activity in blood plasma. The review will briefly discuss all the above-mentioned information, with a description of the current situation in the research

Atherosclerosis in HIV Patients: What Do We Know so Far?

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

Harnessing the Therapeutic Potential of Decoys in Non-Atherosclerotic Cardiovascular Diseases: State of the Art

Cardiovascular disease (CVD) is the main cause of global death, highlighting the fact that conventional therapeutic approaches for the treatment of CVD patients are insufficient, and there is a need to develop new therapeutic approaches. In recent years, decoy technology, decoy oligodeoxynucleotides (ODN), and decoy peptides show promising results for the future treatment of CVDs. Decoy ODN inhibits transcription by binding to the transcriptional factor, while decoy peptide neutralizes receptors by binding to the ligands. This review focused on studies that have investigated the effects of decoy ODN and decoy peptides on non-atherosclerotic CVD

Gold nanoparticles: Multifaceted roles in the management of autoimmune disorders

Gold nanoparticles (GNPs) have been recently applied for various diagnostic and therapeutic purposes. The unique properties of these nanoparticles (NPs), such as relative ease of synthesis in various sizes, shapes and charges, stability, high drug-loading capacity and relative availability for modification accompanied by non-cytotoxicity and biocompatibility, make them an ideal field of research in bio-nanotechnology. Moreover, their potential to alleviate various inflammatory factors, nitrite species, and reactive oxygen production and the capacity to deliver therapeutic agents has attracted attention for further studies in inflammatory and autoimmune disorders. Furthermore, the characteristics of GNPs and surface modification can modulate their toxicity, biodistribution, biocompatibility, and effects. This review discusses in vitro and in vivo effects of GNPs and their functionalized forms in managing various autoimmune disorders (Ads) such as rheumatoid arthritis, type 1 diabetes, and multiple sclerosis