Acquired coagulopathy and complement system pathology in chronic hepatic disorders.

Комплемент и коагуляция являются эволюционно связанными протеолитическими гуморальными системами, которые имеют решающее значение для осуществления врожденного иммунного ответа на повреждение и инфекцию, ограничения кровотечения и патологического тромбообразования. Печень играет центральную роль в функционировании системы гемостаза и комплемента: она синтезирует большинство факторов свертывания и их ингибиторов, а также протеины системы комплимента. При хронических заболеваниях печени нарушения системы гемостаза протекают по типу коагулопатий, выраженность которых будет определять клиническую картину основного заболевания. В обзоре представлены данные о роли сосудисто-тромбоцитарного, коагуляционного, антикоагулянтного и фибринолитического звеньев системы гемостаза и компонентов системы комплемента в патогенезе хронических заболеваний печени. Complement and coagulation are evolutionarily related proteolytic humoral systems that are crucial for the innate immune response to injury and infection, for limiting hemorrhage and pathological thrombosis. The liver plays a central role in the functioning of hemostasis and complement system. It synthesizes most coagulation factors and their inhibitors, as well as complement system proteins. In chronic hepatic diseases, hemostasis disorders proceed as coagulopathies, and their severity determine the clinical picture of basic disease. This review presents data about the role of vascular-platelet, coagulant, anticoagulant and fibrinolytic links of hemostasis and complement system components in the pathogenesis of chronic hepatic diseases.

EPIGENOMIC FACTORS FOR THE DEVELOPMENT OF PERITONEAL ADHESIONS

Summary. The etiology of the development of adhesive disease — the most common postoperative complication — can be determined by epigenomic disorders related to various links of resistance and immunogenetic control. Purpose of the study. To study the epigenomic factors in the development of adhesive disease, the immune status of patients operated on in the abdominal cavity was studied. The comparison group included 55 patients with a complicated course of peritoneal commissural disease, the main group consisted of 59 patients operated on on the abdominal organs on the background of peritoneal commissural disease, the course of which was asymptomatic. Results and its discussion. The revealed epigenomic factors associated with the risk of developing adhesive disease: belongs to an increase in the concentration of acute phase proteins - ceruloplasmin, haptoglobin, C-reactive protein, C3 fragment of the complement system proteins, changes in the expression of adhesion molecule genes (CD31 increased by 10 %, CD54 increased to 24.1 % in comparison with the comparison group — 13.25 %). Conclusions. The results of our studies showed that patients with adhesive disease have a wide range of epigenome trigger factors. Epigenomic factors associated with the risk of developing adhesive disease include an increase in the concentration of acute phase proteins - ceruloplasmin, haptoglobin, C-reactive protein, C3 fragment of the complement system proteins, changes in the expression of adhesion molecule genes (CD31 increased by 10 %, CD54 increased to 24, 1 % compared with the comparison group - 13.25 %)

Proteomic Analysis of Human Serum from Patients with Chronic Kidney Disease

Chronic kidney disease (CKD) is an important public health problem in the world. The aim of our research was to identify novel potential serum biomarkers of renal injury. ELISA assay showed that cytokines and chemokines IL-1β, IL-2, IL-4, IL-5, IL-6, IL-7, IL-8, IL-9, IL-10, IL-12 (p70), IL-13, IL-15, IL-17, Eotaxin, FGFb, G-CSF, GM-CSF, IP-10, MCP-1, MIP-1α, MIP-1β, PDGF-1bb, RANTES, TNF-α and VEGF were significantly higher (R > 0.6, p value < 0.05) in the serum of patients with CKD compared to healthy subjects, and they were positively correlated with well-established markers (urea and creatinine). The multiple reaction monitoring (MRM) quantification method revealed that levels of HSP90B2, AAT, IGSF22, CUL5, PKCE, APOA4, APOE, APOA1, CCDC171, CCDC43, VIL1, Antigen KI-67, NKRF, APPBP2, CAPRI and most complement system proteins were increased in serum of CKD patients compared to the healthy group. Among complement system proteins, the C8G subunit was significantly decreased three-fold in patients with CKD. However, only AAT and HSP90B2 were positively correlated with well-established markers and, therefore, could be proposed as potential biomarkers for CKD.

Molecular Mechanisms of Complement System Proteins and Matrix Metalloproteinases in the Pathogenesis of Age-Related Macular Degeneration

: Age-related macular degeneration (AMD) is an eye disorder affecting predominantly the older people above the age of 50 years in which the macular region of the retina deteriorates, resulting in the loss of central vision. The key factors associated with the pathogenesis of AMD are age, smoking, dietary, and genetic risk factors. There are few associated and plausible genes involved in AMD pathogenesis. Common genetic variants (with a minor allele frequency of >5% in the population) near the complement genes explain 40–60% of the heritability of AMD. The complement system is a group of proteins that work together to destroy foreign invaders, trigger inflammation, and remove debris from cells and tissues. Genetic changes in and around several complement system genes, including the CFH, contribute to the formation of drusen and progression of AMD. Similarly, Matrix metalloproteinases (MMPs) that are normally involved in tissue remodeling also play a critical role in the pathogenesis of AMD. MMPs are involved in the degradation of cell debris and lipid deposits beneath retina but with age their functions get affected and result in the drusen formation, succeeding to macular degeneration. In this review, AMD pathology, existing knowledge about the normal and pathological role of complement system proteins and MMPs in the eye is reviewed. The scattered data of complement system proteins, MMPs, drusenogenesis, and lipofusogenesis have been gathered and discussed in detail. This might add new dimensions to the understanding of molecular mechanisms of AMD pathophysiology and might help in finding new therapeutic options for AMD.

AFM study of complement system assembly initiated by antigen-antibody complex

The shape and size of complement system C1 components assembled on a SiO2 surface after classical activation by antigen-antibody complex was determined by tapping mode atomic force microscopy (AFM). The SiO2 substrate was silanized and bovine leukemia virus proteins gp51 were covalently bound to the SiO2 substrate. Self-assembly of complement system proteins was investigated by AFM. Uniform coating of silanized surface by gp51 proteins was observed by AFM. After incubation of gp51 coated substrate in anti-gp51 antibody containing solution, Ag-Ab complexes were detected on the substrate surface by AFM. Then after treatment of Ag-Ab complex modified substrate by guinea-pig blood serum containing highly active complement system proteins for 3 minutes and 30 minutes features 2–3 times and 5–8 times higher in diameter and in height if compared with those observed after formation of Ag-Ab complex, were observed respectively on the surface of SiO2. This study revealed that AFM might be applied for the imaging of complement system assembly and provides valuable information that can be used to complement other well-established techniques.