Role of ABCA1 in Atherosclerosis: Novel Mutations and Potential Plant-derived Therapies.

ATP-binding cassette transporter A1 (ABCA1) is one of the key proteins regulating cholesterol homeostasis and playing a crucial role in atherosclerosis development. ABCA1 regulates the rate-limiting step of reverse cholesterol transport, facilitates the efflux of surplus intracellular cholesterol and phospholipids, and suppresses inflammation through several signalling pathways. At the same time, many mutations and Single Nucleotide Polymorphisms (SNPs) have been identified in the ABCA1 gene, which affects its biological function and is associated with several hereditary diseases (such as familial hypo-alpha-lipoproteinaemia and Tangier disease) and increased risk of cardiovascular diseases (CVDs). This review summarises recently identified mutations and SNPs in their connection to atherosclerosis and associated CVDs. Also, we discuss the recently described application of various plant-derived compounds to modulate ABCA1 expression in different in vitro and in vivo models. Herein, we present a comprehensive overview of the association of ABCA1 mutations and SNPs with CVDs and as a pharmacological target for different natural-derived compounds and highlight the potential application of these phytochemicals for treating atherosclerosis through modulation of ABCA1 expression.

The Physiological and Molecular Mechanisms of Silicon Action in Salt Stress Amelioration.

Salinity is one of the most common abiotic stress factors affecting different biochemical and physiological processes in plants, inhibiting plant growth, and greatly reducing productivity. During the last decade, silicon (Si) supplementation was intensively studied and now is proposed as one of the most convincing methods to improve plant tolerance to salt stress. In this review, we discuss recent papers investigating the role of Si in modulating molecular, biochemical, and physiological processes that are negatively affected by high salinity. Although multiple reports have demonstrated the beneficial effects of Si application in mitigating salt stress, the exact molecular mechanism underlying these effects is not yet well understood. In this review, we focus on the localisation of Si transporters and the mechanism of Si uptake, accumulation, and deposition to understand the role of Si in various relevant physiological processes. Further, we discuss the role of Si supplementation in antioxidant response, maintenance of photosynthesis efficiency, and production of osmoprotectants. Additionally, we highlight crosstalk of Si with other ions, lignin, and phytohormones. Finally, we suggest some directions for future work, which could improve our understanding of the role of Si in plants under salt stress.

Recent Updates on ALMT Transporters' Physiology, Regulation, and Molecular Evolution in Plants.

Aluminium toxicity and phosphorus deficiency in soils are the main interconnected problems of modern agriculture. The aluminium-activated malate transporters (ALMTs) comprise a membrane protein family that demonstrates various physiological functions in plants, such as tolerance to environmental Al3+ and the regulation of stomatal movement. Over the past few decades, the regulation of ALMT family proteins has been intensively studied. In this review, we summarise the current knowledge about this transporter family and assess their involvement in diverse physiological processes and comprehensive regulatory mechanisms. Furthermore, we have conducted a thorough bioinformatic analysis to decipher the functional importance of conserved residues, structural components, and domains. Our phylogenetic analysis has also provided new insights into the molecular evolution of ALMT family proteins, expanding their scope beyond the plant kingdom. Lastly, we have formulated several outstanding questions and research directions to further enhance our understanding of the fundamental role of ALMT proteins and to assess their physiological functions.

The role of centromeric repeats and transcripts in kinetochore assembly and function.

Centromeres are the chromosomal domains, where the kinetochore protein complex is formed, mediating proper segregation of chromosomes during cell division. Although the function of centromeres has remained conserved during evolution, centromeric DNA is highly variable, even in closely related species. In addition, the composition of the kinetochore complexes varies among organisms. Therefore, it is assumed that the centromeric position is determined epigenetically, and the centromeric histone H3 (CENH3) serves as an epigenetic marker. The loading of CENH3 onto centromeres depends on centromere-licensing factors, chaperones, and transcription of centromeric repeats. Several proteins that regulate CENH3 loading and kinetochore assembly interact with the centromeric transcripts and DNA in a sequence-independent manner. However, the functional aspects of these interactions are not fully understood. This review discusses the variability of centromeric sequences in different organisms and the regulation of their transcription through the RNA Pol II and RNAi machinery. The data suggest that the interaction of proteins involved in CENH3 loading and kinetochore assembly with centromeric DNA and transcripts plays a role in centromere, and possibly neocentromere, formation in a sequence-independent manner.

Potential Application of the Plant-Derived Essential Oils for Atherosclerosis Treatment: Molecular Mechanisms and Therapeutic Potential.

Essential oils (EOs) are complex secondary metabolites identified in many plant species. Plant-derived EOs have been widely used in traditional medicine for centuries for their health-beneficial effects. Some EOs and their active ingredients have been reported to improve the cardiovascular system, in particular to provide an anti-atherosclerotic effect. The objective of this review is to highlight the recent research investigating the anti-inflammatory, anti-oxidative and lipid-lowering properties of plant-derived EOs and discuss their mechanisms of action. Also, recent clinical trials exploring anti-inflammatory and anti-oxidative activities of EOs are discussed. Future research on EOs has the potential to identify new bioactive compounds and invent new effective agents for treatment of atherosclerosis and related diseases such as diabetes, metabolic syndrome and obesity.

Mitochondria-derived peptides in healthy ageing and therapy of age-related diseases.

Mitochondrial-derived peptides (MDPs) are small bioactive peptides encoded by mitochondrial DNA and involved in various stress-protecting mechanisms. To date, eight mitochondrial-derived peptides have been identified: MOTS-c sequence is hidden in the 12 S rRNA gene (MT-RNR1), and the other 7 (humanin and small humanin-like peptides 1-6) are encoded by the 16 S rRNA (MT-RNR2) gene. While the anti-apoptotic, anti-inflammatory and cardioprotective activities of MDPs are well described, recent research suggests that MDPs are sensitive metabolic sensors, closely connected with mtDNA mutation-associated diseases and age-associated metabolic disorders. In this chapter, we focus on the recent progress in understanding the metabolo-protective properties of MDPs, their role in maintenance of the cellular and mitochondrial homeostasis associated with age-related diseases: Alzheimer's disease, cognitive decline, macular degeneration and cataracts. Also, we will discuss MDPs-based and MDPs-targeted interventions to treat age-related diseases and extend a healthy lifespan.

Oligosaccharides as Potential Therapeutics against Atherosclerosis.

Atherosclerosis is the major cause of cardiovascular-disease-related death worldwide, resulting from the subendothelial accumulation of lipoprotein-derived cholesterol, ultimately leading to chronic inflammation and the formation of clinically significant atherosclerotic plaques. Oligosaccharides have been widely used in biomedical research and therapy, including tissue engineering, wound healing, and drug delivery. Moreover, oligosaccharides have been consumed by humans for centuries, and are cheap, and available in large amounts. Given the constantly increasing number of obesity, diabetes, and hyperlipidaemia cases, there is an urgent need for novel therapeutics that can economically and effectively slow the progression of atherosclerosis. In this review, we address the current state of knowledge in oligosaccharides research, and provide an update of the recent in vitro and in vivo experiments that precede clinical studies. The application of oligosaccharides could help to eliminate the residual risk after the application of other cholesterol-lowering medicines, and provide new therapeutic opportunities to reduce the associated burden of premature deaths because of atherosclerosis.

The Role of Selenium in Atherosclerosis Development, Progression, Prevention and Treatment.

Selenium is an essential trace element that is essential for various metabolic processes, protection from oxidative stress and proper functioning of the cardiovascular system. Se deficiency has long been associated with multiple cardiovascular diseases, including endemic Keshan's disease, common heart failure, coronary heart disease, myocardial infarction and atherosclerosis. Through selenoenzymes and selenoproteins, Se is involved in numerous crucial processes, such as redox homeostasis regulation, oxidative stress, calcium flux and thyroid hormone metabolism; an unbalanced Se supply may disrupt these processes. In this review, we focus on the importance of Se in cardiovascular health and provide updated information on the role of Se in specific processes involved in the development and pathogenesis of atherosclerosis (oxidative stress, inflammation, endothelial dysfunction, vascular calcification and vascular cell apoptosis). We also discuss recent randomised trials investigating Se supplementation as a potential therapeutic and preventive agent for atherosclerosis treatment.

The Role of Anthocyanins in Plant Tolerance to Drought and Salt Stresses.

Drought and salinity affect various biochemical and physiological processes in plants, inhibit plant growth, and significantly reduce productivity. The anthocyanin biosynthesis system represents one of the plant stress-tolerance mechanisms, activated by surplus reactive oxygen species. Anthocyanins act as ROS scavengers, protecting plants from oxidative damage and enhancing their sustainability. In this review, we focus on molecular and biochemical mechanisms underlying the role of anthocyanins in acquired tolerance to drought and salt stresses. Also, we discuss the role of abscisic acid and the abscisic-acid-miRNA156 regulatory node in the regulation of drought-induced anthocyanin production. Additionally, we summarise the available knowledge on transcription factors involved in anthocyanin biosynthesis and development of salt and drought tolerance. Finally, we discuss recent progress in the application of modern gene manipulation technologies in the development of anthocyanin-enriched plants with enhanced tolerance to drought and salt stresses.

The regulation of plant cell wall organisation under salt stress.

Plant cell wall biosynthesis is a complex and tightly regulated process. The composition and the structure of the cell wall should have a certain level of plasticity to ensure dynamic changes upon encountering environmental stresses or to fulfil the demand of the rapidly growing cells. The status of the cell wall is constantly monitored to facilitate optimal growth through the activation of appropriate stress response mechanisms. Salt stress can severely damage plant cell walls and disrupt the normal growth and development of plants, greatly reducing productivity and yield. Plants respond to salt stress and cope with the resulting damage by altering the synthesis and deposition of the main cell wall components to prevent water loss and decrease the transport of surplus ions into the plant. Such cell wall modifications affect biosynthesis and deposition of the main cell wall components: cellulose, pectins, hemicelluloses, lignin, and suberin. In this review, we highlight the roles of cell wall components in salt stress tolerance and the regulatory mechanisms underlying their maintenance under salt stress conditions.

The Role of Pericytes in Regulation of Innate and Adaptive Immunity.

Pericytes are perivascular multipotent cells wrapping microvascular capillaries, where they support vasculature functioning, participate in tissue regeneration, and regulate blood flow. However, recent evidence suggests that in addition to traditionally credited structural function, pericytes also manifest immune properties. In this review, we summarise recent data regarding pericytes' response to different pro-inflammatory stimuli and their involvement in innate immune responses through expression of pattern-recognition receptors. Moreover, pericytes express various adhesion molecules, thus regulating trafficking of immune cells across vessel walls. Additionally, the role of pericytes in modulation of adaptive immunity is discussed. Finally, recent reports have suggested that the interaction with cancer cells evokes immunosuppression function in pericytes, thus facilitating immune evasion and facilitating cancer proliferation and metastasis. However, such complex and multi-faceted cross-talks of pericytes with immune cells also suggest a number of potential pericyte-based therapeutic methods and techniques for cancer immunotherapy and treatment of autoimmune and auto-inflammatory disorders.

Recent updates on the physiology and evolution of plant TPK/KCO channels.

Plant vacuoles are the main cellular reservoirs to store K+ . The vacuolar K+ channels play a pivotal role in K+ exchange between cytosol and vacuolar sap. Among vacuolar K+ transporters, the Two Pore Potassium Channels (TPKs) are highly selective K+ channels present in most or all plant vacuoles and could be involved in various plant stress responses and developmental processes. Although the majority of TPK members have a vacuolar specialisation, some TPKs display different membrane localisation including the plasma membrane, tonoplast of protein storage vacuoles and probably chloroplast membranes. The functional properties as well as physiological roles of TPKs remains largely unexplored. In this review, we have collected recent data about the physiology, structure, functionality and evolution of TPK/KCO3 channels. We also critically evaluate the latest findings on the biological role, physiological functions, and regulation of TPK/KCO3 channels in relation to their structure and phylogenetic position. The possible role of TPK/KCO3 channels in plant tolerance to various abiotic stresses is summarised, and the future priority directions for TPK/KCO3 studies are addressed.

Metabolites Facilitating Adaptation of Desert Cyanobacteria to Extremely Arid Environments.

Desert is one of the harshest environments on the planet, characterized by exposure to daily fluctuations of extreme conditions (such as high temperature, low nitrogen, low water, high salt, etc.). However, some cyanobacteria are able to live and flourish in such conditions, form communities, and facilitate survival of other organisms. Therefore, to ensure survival, desert cyanobacteria must develop sophisticated and comprehensive adaptation strategies to enhance their tolerance to multiple simultaneous stresses. In this review, we discuss the metabolic pathways used by desert cyanobacteria to adapt to extreme arid conditions. In particular, we focus on the extracellular polysaccharides and compatible solutes biosynthesis pathways and their evolution and special features. We also discuss the role of desert cyanobacteria in the improvement of soil properties and their ecological and environmental impact on soil communities. Finally, we summarize recent achievements in the application of desert cyanobacteria to prevent soil erosion and desertification.

Emerging role of pericytes in therapy of cardiovascular diseases.

Pericytes are mural vascular cells covering microvascular capillaries, where they contribute to the formation, maturation, maintenance, stabilisation and remodelling of vasculature. They actively interact and communicate with other cells to maintain the capillary structural integrity, vascular permeability and blood flow. Pericytes are crucial participants in the physiological and pathological processes of cardiovascular disease. In this review, we summarise recent data regarding pericyte metabolism, trans-differentiation, angiogenesis and immunomodulation in connection with different cardiovascular pathologies. Further, we discuss an application of pericytes as a new cell therapy approach to treat coronary artery disease, congenital heart disease, atherosclerotic plaques calcification and calcific valvular heart disease in different in vivo animal models and in vitro studies. Also, we discuss different methods and pharmacological therapies for CVDs treatment with pericyte-mediated effects. Finally, we present a comprehensive overview of the role of pericytes in CVDs and as a pharmacological target for different novel drugs and techniques and highlight the potential application of pericytes to treat CVDs.

Molecular Mechanisms Underlying Pathological and Therapeutic Roles of Pericytes in Atherosclerosis.

Pericytes are multipotent mesenchymal stromal cells playing an active role in angiogenesis, vessel stabilisation, maturation, remodelling, blood flow regulation and are able to trans-differentiate into other cells of the mesenchymal lineage. In this review, we summarised recent data demonstrating that pericytes play a key role in the pathogenesis and development of atherosclerosis (AS). Pericytes are involved in lipid accumulation, inflammation, growth, and vascularization of the atherosclerotic plaque. Decreased pericyte coverage, endothelial and pericyte dysfunction is associated with intraplaque angiogenesis and haemorrhage, calcification and cholesterol clefts deposition. At the same time, pericytes can be used as a novel therapeutic target to promote vessel maturity and stability, thus reducing plaque vulnerability. Finally, we discuss recent studies exploring effective AS treatments with pericyte-mediated anti-atherosclerotic, anti-inflammatory and anti-apoptotic effects.

The Role of Mitochondrial Abnormalities in Diabetic Cardiomyopathy.

Diabetic cardiomyopathy (DCM) is defined as the presence in diabetic patients of abnormal cardiac structure and performance (such as left ventricular hypertrophy, fibrosis, and arrhythmia) in the absence of other cardiac risk factors (such as hypertension or coronary artery disease). Although the pathogenesis of DCM remains unclear currently, mitochondrial structural and functional dysfunctions are recognised as a central player in the DCM development. In this review, we focus on the role of mitochondrial dynamics, biogenesis and mitophagy, Ca2+ metabolism and bioenergetics in the DCM development and progression. Based on the crucial role of mitochondria in DCM, application of mitochondria-targeting therapies could be effective strategies to slow down the progression of the disease.

Evolution of the Membrane Transport Protein Domain.

Membrane transport proteins are widely present in all living organisms, however, their function, transported substrate, and mechanism of action are unknown. Here we use diverse bioinformatics tools to investigate the evolution of MTPs, analyse domain organisation and loop topology, and study the comparative alignment of modelled 3D structures. Our results suggest a high level of conservancy between MTPs from different taxa on both amino acids and structural levels, which imply some degree of functional similarities. The presence of loop/s of different lengths in various positions suggests tax-on-specific adaptation to transported substrates, intracellular localisation, accessibility for post-translation modifications, and interaction with other proteins. The comparison of modelled structures proposes close relations and a common origin for MTP and Na/H exchanger. Further, a high level of amino acid similarity and identity between archaeal and bacterial MTPs and Na/H exchangers imply conservancy of ion transporting function at least for archaeal and bacterial MTPs.

Interplay between Zn2+ Homeostasis and Mitochondrial Functions in Cardiovascular Diseases and Heart Ageing.

Zinc plays an important role in cardiomyocytes, where it exists in bound and histochemically reactive labile Zn2+ forms. Although Zn2+ concentration is under tight control through several Zn2+-transporters, its concentration and intracellular distribution may vary during normal cardiac function and pathological conditions, when the protein levels and efficacy of Zn2+ transporters can lead to zinc re-distribution among organelles in cardiomyocytes. Such dysregulation of cellular Zn2+ homeostasis leads to mitochondrial and ER stresses, and interrupts normal ER/mitochondria cross-talk and mitophagy, which subsequently, result in increased ROS production and dysregulated metabolic function. Besides cardiac structural and functional defects, insufficient Zn2+ supply was associated with heart development abnormalities, induction and progression of cardiovascular diseases, resulting in accelerated cardiac ageing. In the present review, we summarize the recently identified connections between cellular and mitochondrial Zn2+ homeostasis, ER stress and mitophagy in heart development, excitation-contraction coupling, heart failure and ischemia/reperfusion injury. Additionally, we discuss the role of Zn2+ in accelerated heart ageing and ageing-associated rise of mitochondrial ROS and cardiomyocyte dysfunction.

Mitochondria-Mediated Cardiovascular Benefits of Sodium-Glucose Co-Transporter 2 Inhibitors.

Several recent cardiovascular trials of SGLT 2 (sodium-glucose cotransporter 2) inhibitors revealed that they could reduce adverse cardiovascular events in patients with T2DM (type 2 diabetes mellitus). However, the exact molecular mechanism underlying the beneficial effects that SGLT2 inhibitors have on the cardiovascular system is still unknown. In this review, we focus on the molecular mechanisms of the mitochondria-mediated beneficial effects of SGLT2 inhibitors on the cardiovascular system. The application of SGLT2 inhibitors ameliorates mitochondrial dysfunction, dynamics, bioenergetics, and ion homeostasis and reduces the production of mitochondrial reactive oxygen species, which results in cardioprotective effects. Herein, we present a comprehensive overview of the impact of SGLT2 inhibitors on mitochondria and highlight the potential application of these medications to treat both T2DM and cardiovascular diseases.

Role of the mtDNA Mutations and Mitophagy in Inflammaging.

Ageing is an unavoidable multi-factorial process, characterised by a gradual decrease in physiological functionality and increasing vulnerability of the organism to environmental factors and pathogens, ending, eventually, in death. One of the most elaborated ageing theories implies a direct connection between ROS-mediated mtDNA damage and mutations. In this review, we focus on the role of mitochondrial metabolism, mitochondria generated ROS, mitochondrial dynamics and mitophagy in normal ageing and pathological conditions, such as inflammation. Also, a chronic form of inflammation, which could change the long-term status of the immune system in an age-dependent way, is discussed. Finally, the role of inflammaging in the most common neurodegenerative diseases, such as Alzheimer's and Parkinson's, is also discussed.