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Background: Atherosclerosis is a chronic disease characterized by the increased infiltration and retention of LDL particles in arterial walls. There are several mechanisms underlying atherogenesis, with the pro-atherogenic modifications of LDL playing a significant role. One such modification of native LDL is desialylation, which is characterized by the removal of terminal sialic acid from ApoB-100 glycans that induces critical changes in the overall functionality of the LDL particle., Aims: The aim of this study was to model the desialylation of native LDL in mice, resembling a phenomenon previously observed in atherosclerotic patients., Objective: LDL desialylation was induced in C57BL/6J mice via the injection of exogenous neuraminidase. The degree of LDL desialylation and its duration were assessed. The impact of LDL desialylation on blood lipid levels was evaluated. Furthermore, the morphological alterations in the aorta during LDL desialylation in the bloodstream were examined., Method: The control group of C57BL/6J mice received saline injections, while the experimental group underwent a single injection of IgG-conjugated Vibrio cholerae neuraminidase. The LDL sialic acid levels were assessed 1-7 days post-injection using the Warren method and normalized to total protein content measured via the Lowry method. A similar protocol was followed for the subchronic administration of the IgG-neuraminidase conjugate over a 6-week period. The blood lipid profiles were analyzed using commercial kits. The atherosclerotic plaque burden in the mouse aorta was quantified using Oil Red O and hematoxylin-eosin staining., Result: A single administration of 20 mU IgG-neuraminidase conjugate resulted in decreased LDL sialic acid levels for 5 days, gradually recovering by days 6-7. Subchronic administration maintained reduced LDL sialic acid levels for up to 2 months. Notably, sustained LDL desialylation was associated with elevated LDL cholesterol levels., Conclusion: A sustained desialylation of LDL in C57BL/6J mice was achieved through subchronic administration of IgG-conjugated neuraminidase. This study provides an approach for sustained LDL desialylation in mice. Further studies using apolipoprotein E knockout mice and LDL desialylation will reveal the role of this process in the occurrence and development of atherosclerosis., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Atherosclerotic cardiovascular disease (ASCVD) is an advanced chronic inflammatory disease and the leading cause of death worldwide. The pathological development of ASCVD begins with atherosclerosis, characterised by a pathological remodelling of the arterial wall, lipid accumulation and build-up of atheromatous plaque. As the disease advances, it narrows the vascular lumen and limits the blood, leading to ischaemic necrosis in coronary arteries. Exosomes are nano-sized lipid vesicles of different origins that can carry many bioactive molecules from their parental cells, thus playing an important role in intercellular communication. The roles of exosomes in atherosclerosis have recently been intensively studied, advancing our understanding of the underlying molecular mechanisms. In this review, we briefly introduce exosome biology and then focus on the roles of exosomes of different cellular origins in atherosclerosis development and progression, functional significance of their cargoes and physiological impact on recipient cells. Studies have demonstrated that exosomes originating from endothelial cells, vascular smooth muscle cells, macrophages, dendritic cells, platelets, stem cells, adipose tissue and other sources play an important role in the atherosclerosis development and progression by affecting cholesterol transport, inflammatory, apoptotic and other aspects of the recipient cells' metabolism. MicroRNAs are considered the most significant type of bioactive molecules transported by exosomes and involved in ASCVD development. Finally, we review the current achievements and limitations associated with the use of exosomes for the diagnosis and treatment of ASCVD., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Osteoarthritis (OA) is the most common degenerative joint disease causing pain and functional limitations. Physical activity as a clinically relevant, effective intervention alleviates pain and promotes joint function. In chondrocytes, perception and transmission of mechanical signals are controlled by mechanosensitive ion channels, whose dysfunction in OA chondrocytes is leading to disease progression. Signaling of mechanosensitive ion channels Piezo/TRPV4 was analyzed by Yoda1/GSK1016790A application and calcium-imaging of Fura-2-loaded chondrocytes. Expression analysis was determined by qPCR and immunofluorescence in healthy vs. OA chondrocytes. Chondrocytes were mechanically stimulated using the Flexcell™ technique. Yoda1 and GSK1016790A caused an increase in intracellular calcium [Ca 2+ ] i for Yoda1, depending on extracellularly available Ca 2+ . When used concomitantly, the agonist applied first inhibited the effect of subsequent agonist application, indicating mutual interference between Piezo/TRPV4. Yoda1 increased the expression of metalloproteinases, bone-morphogenic protein, and interleukins in healthy and OA chondrocytes to a different extent. Flexcell™-induced changes in the expression of MMPs and ILs differed from changes induced by Yoda1. We conclude that Piezo1/TRPV4 communicate with each other, an interference that may be impaired in OA chondrocytes. It is important to consider that mechanical stimulation may have different effects on OA depending on its intensity.

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.

Diabetes mellitus and related complications are among the most important problems of the world-leading healthcare systems. Despite their priority, molecular and genetic aspects of diabetes pathogenesis are poorly understood; however, the involvement of oxidative stress in this process is undoubted. Rats with experimental diabetes induced by the intraperitoneal injection of alloxan were subjected to the antioxidant pre-therapy with a series of mitochondria-targeted 10-(6'-plastoquinonyl)decyltriphenylphosphonium (SkQ1) injections and analyzed for the expression of mRNAs and microRNAs by real-time quantitative polymerase chain reaction to identify potential predictors of diabetes. Animals that received SkQ1 before diabetes induction demonstrated lower blood glucose levels compared to the diabetic animals not subjected to the therapy. SkQ1 caused changes in the mRNA levels of genes involved in the cellular defense against free radicals, which indicates a beneficial effect of the pre-therapy. Moreover, similar changes were observed on the epigenetic level, as the microRNA expression patterns not only proved the SkQ1 efficacy but also correlated with the expression levels of their mRNA targets. Oxidative stress and macromolecule damage by free radicals are determining factors in diabetes, which suggests that strategies aimed at restoring the antioxidant status of the cell can be beneficial. Mitochondria-targeted antioxidant SkQ1 demonstrates positive effects on several levels, from the normalization of the blood glucose content to genetic and epigenetic changes. Our results can serve as a basis for the development of novel therapeutic and diagnostic strategies.

Macrophages are key players in human innate immunity that protect the organism from pathologic agents, including infection and malignant cells. The spectrum of their functions includes initiation and maintaining of inflammation, cleaning of pathogens and cell debris, as well as inflammation resolution and tissue remodeling and repair. Such a wide spectrum is reflected by the great variety of macrophage phenotypes based on the activation of distinct transcription patterns in response to different stimuli. Studying this complexity requires an integrated approach, such as transcriptome studies. For many genes, the exact role in macrophage biology remains unknown, although clear associations with pro- or anti-inflammatory macrophage polarization could be demonstrated. These findings reveal the novel directions for future research. In this review, we describe the known mechanisms of macrophage polarization and the new insights available from transcriptome studies., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Background: Although the coagulation system is evolutionary well preserved, profound species differences exist in viscoelastic as well as in common laboratory tests of coagulation., Objective: Evaluating differences in clot formation and material characterisation of clots of four mammalian species on macro-, micro- and nanoscales by the means of rheometry, scanning electron microscopy (SEM) and small angle x-ray scattering (SAXS)., Methods: Blood samples were collected from healthy human volunteers, laboratory rats (HL/LE inbred strain), warmblood horses and dromedary camels. Clot formation was observed by oscillating shear rheometry until plateau formation of the shear storage modulus G', at which point selected clots were prepared for scanning electron microscopy. SEM images were analysed for fibre diameter and fractal dimension. Additionally, scattering profiles for plasma and whole blood samples were obtained with SAXS., Results: Viscoelasticity of clots showed great interspecies variation: clots of rats and horses exhibited shorter clotting times and higher G' plateau values, when compared to human clots. Camel clots showed unique clotting characteristics with no G' plateau formation in the timeframe observed. Less differentiating features were found with SEM and SAXS, although the rat fibre network appears to be more convoluted and dense, which resulted in a higher fractal dimension., Conclusion: Clotting kinetic differs between the species, which is not only of clinical interest, but could also be an important finding for animal models of blood coagulation.