Novel Insights Into the Role of Glycans in the Pathophysiology of Glomerular Endotheliosis in Preeclampsia

ABSTARCT: The polysaccharide heparan sulfate is ubiquitously expressed as a proteoglycan in extracellular matrices and on cell surfaces. In the glomerular filtration barrier, the action of the heparan sulfate is directly related to the function of glomerular filtration, mostly attributed to the sulfated domains that occur along the polysaccharide chain, as evidenced by fact that release of fragments of heparan sulfate by heparanase significantly increases the permeability of albumin passage through the glomerular endothelium, event that originates proteinuria. This review aims to show the importance of the structural domains of heparan sulfate in the process of selective permeability and to demonstrate how these domains may be altered during the glomerular inflammation processes that occur in preeclampsia

The pathogenetic role of glycoproteins and proteoglycans in dog glomerulonephritis

The aim: to determine the main pathogenetic links of glomerulonephritis in dogs with the participation of connective tissue biopolymers. Materials and methods The research was conducted by analyzing the sources of scientific literature (PubMed, Elsevier, electronic resources of the V. I. Vernadskyi National Library) and the clinical experience of the authors, thanks to which a scheme of the pathogenesis of glomerulonephritis in dogs with the participation of connective tissue biopolymers was developed. Results. According to the results of our research, it was established, that chronic glomerulonephritis in dogs is accompanied by neutrophilia, lymphocytosis, as well as urinary and nephrotic syndromes, the progression of which causes a violation of the functional state of the kidneys and liver. Sick dogs develop a nephrotic symptom complex – persistent proteinuria, hypoalbuminemia, dysproteinemia, and hyperlipidemia. Clinically, edema was not observed, because it is known, that in dogs they are rarely detected with nephrotic syndrome. Inflammation in the kidneys is accompanied by an increase in the concentration of glycoproteins and sialic acids in the blood serum. After treatment, there was a decrease in the inflammatory process in the kidneys, which was manifested by a decrease in neutrophilia and lymphocytosis, as well as the content of glycoproteins and sialic acids in the blood serum. The content of total chondroitin sulfates and the fractional composition of glycosaminoglycans did not change, and the level of excretion of oxyproline and uronic acids decreased compared to the indicators before the start of treatment. This, in our opinion, is due to the slowing down of fibrotic processes in the kidneys. Thus, biochemical indicators of the state of connective tissue in the blood serum and urine of dogs with glomerulonephritis allowed us to evaluate the functional state of the kidneys for their inflammation (oxyproline and uronic acids), as well as to determine the violation of proteoglycan synthesis in nephrotic syndrome. Conclusions. For glomerulonephritis in dogs on the background of depression, decreased appetite, polydipsia, pain during palpation in the lumbar region, periodic vomiting, neutrophilic leukocytosis, lymphocytosis, nephrotic syndrome (hypoalbuminemia, increase in α2- and β-globulins, cholesterol, β-lipoproteins), growth activity of ALT, AST, and alkaline phosphatase, a decrease in Veltman's test, hyperazotemia, hyperphosphatemia, proteinuria, microhematuria, and cylindruria, there is an increase in the content of glycoproteins, sialic acids, and chondroitin sulfates, as well as heparan sulfate in the blood serum of dogs. The increase in the blood serum of patients with canine glomerulonephritis, as a marker of connective tissue – glycoproteins, sialic acids, chondroitinsulfates, and urinary excretion of oxyproline and uronic acids is due to inflammatory and fibrotic changes in the basal membranes of the kidney glomerul

Alternative pathway activation in pregnancy, a measured amount “complements” a successful pregnancy, too much results in adverse events

Summary: During pregnancy, the maternal host must adapt in order to enable growth of the fetus. These changes affect all organ systems and are designed both to protect the fetus and to minimize risk to the mother. One of the most prominent adaptations involves the immune system. The semi‐allogenic fetoplacental unit has non‐self components and must be protected against attack from the host. This requires both attenuation of adaptive immunity and protection from innate immune defense mechanisms. One of the key innate immune players is complement, and it is important that the fetoplacental unit is not identified as non‐self and subjected to complement attack. Adaptation of the complement response must, however, be managed in such a way that maternal protection against infection is not compromised. As the complement system also plays a significant facilitating role in many of the stages of a normal pregnancy, it is also important that any necessary adaptation to accommodate the semi‐allogenic aspects of the fetoplacental unit does not compromise this. In this review, both the physiological role of the alternative pathway of complement in facilitating a normal pregnancy, and its detrimental participation in pregnancy‐specific disorders, are discussed

Preeclampsia

Preeclampsia is a disorder of pregnancy characterized by high blood pressure, edema, and proteinuria that affects 2%–8% of pregnancies worldwide. Hypertensive disorders of pregnancy, including preeclampsia, are among the most common causes of death in pregnant persons. Over six chapters, this book examines the pathophysiology of preeclampsia, vitamin D deficiency as a risk factor for preeclampsia, the cellular changes that occur with preeclampsia, associated organ dysfunction, gestational endotheliopathy, and ophthalmic complications of preeclampsia

Kidney Inflammation, Injury and Regeneration 2020

Acute kidney injury (AKI) is still associated with high morbidity and mortality incidence rates, and also bears an elevated risk of chronic kidney disease in the sequel. Whereas the kidney has a remarkable capacity for regeneration after injury and may recover completely depending on the type of renal lesions, the options for clinical intervention are restricted to fluid management and extracorporeal kidney support. The development of novel therapies to prevent AKI, to improve renal regeneration capacity after AKI, and to preserve renal function—in both the short- and long-term—is urgently needed. This Special Issue includes papers investigating the pathological mechanisms of renal inflammation and AKI and diagnostics using new biomarkers. Furthermore, experimental in vitro and in vivo studies examining potential new approaches to attenuate kidney dysfunction are included, as well as review articles

Molecular and Cellular Mechanisms of Preeclampsia

This Special Issue on the “Molecular and Cellular Mechanisms of Preeclampsia” belongs to the section “Molecular Pathology, Diagnostics, and Therapeutics” of the International Journal of Molecular Sciences. It was a very successful Special Issue as it contains 20 published papers, including one editorial, nine original research papers, and ten reviews on the topic. The original publications cover a wide spectrum of topics, including alterations and involvement of specific factors during preeclampsia, new non-invasive technologies to identify changes, new treatment options, animal models, gender aspects, and effects of the pregnancy pathology later in life. The review publications again cover a wide spectrum of topics, including factors and pathways involved in preeclampsia, effects on the maternal vascular and immune systems, effects on the placenta and the trophoblast, epigenetic changes, new preventive strategies, and new views on the current hypotheses on preeclampsia. Taken together, this Special Issue gives a fantastic overview on a broad spectrum of topics, all of which are important to identify the real etiology of preeclampsia and to finally develop real treatment options