The activity of matrix metalloproteinases and the concentration of their tissue inhibitors in the blood serum of patients with type 2 diabetes mellitus, depending on the stage of compensation of the disease

The aim of the study was to test the hypothesis on the possible reason for the decrease in the activity of matrix metalloproteinases (MMPs) as a consequence of the high concentration of their tissue inhibitors (TIMPs) in the blood serum of patients with type 2 diabetes mellitus (T2DM). Material and methods. In the experimental part of the article, we used the blood serum of patients under observation in the clinic of the Federal Research Center of Fundamental and Translational Medicine. According to the content of glycated hemoglobin (HbA1С) in blood serum, the patients were divided into 3 groups: at the stage of compensation (6.0–6.5 % HbA1С), at the stage of subcompensation (6.6–7.0 % HbA 1С) and decompensation (> 7.0 % HbA1С). The activity of MMPs 2 and 7 in blood serum samples was measured by a fluorimetric method using a fluorescent substrate specific for these MMPs. The concentration of TIMP-1 (inhibitor of all non-membrane-bound MMPs) and TIMP-2 (active against MMP-2 and -7) in blood serum were determined by enzyme immunoassay. Results and discussion. In patients with T2DM, the MMP-2 and -7 activities decreased, more pronouncedly at the stage of decompensation. An increase in the concentration of TIMP-1 was observed in the serum of all patients, while no significant changes in the content of TIMP-2 were found. At the stage of decompensation, a decrease in MMP activity was accompanied by a decrease in the content of insulin, C-peptide and a corresponding increase in the level of proinsulin. An inverse correlation was found between the concentrations of TIMP-1 and insulin in patients at the stage of decompensation of T2DM. It is assumed that the activity of MMP-2 and -7, in comparison with their inhibitors, forms stronger correlations with the parameters of carbohydrate metabolism

Coagulatory defects in type-1 and type-2 diabetes

This research was funded by British Heart Foundation, grant numbers PG/15/9/31270 and FS/15/42/31556.Diabetes (both type-1 and type-2) affects millions of individuals worldwide. A major cause of death for individuals with diabetes is cardiovascular diseases, in part since both types of diabetes lead to physiological changes that affect haemostasis. Those changes include altered concentrations of coagulatory proteins, hyper-activation of platelets, changes in metal ion homeostasis, alterations in lipid metabolism (leading to lipotoxicity in the heart and atherosclerosis), the presence of pro-coagulatory microparticles and endothelial dysfunction. In this review, we explore the different mechanisms by which diabetes leads to an increased risk of developing coagulatory disorders and how this differs between type-1 and type-2 diabetes.Publisher PDFPeer reviewe

Atherosclerosis

The first national conference with international participation, “Fundamental aspects of atherosclerosis: scientific research for improving the technologies of personalized medicine”, was held in Novosibirsk on 15 October, 2021. The purpose of this conference was to disseminate the latest basic and clinical findings in the fields of etiology, clinical characteristics, and modern diagnostics and treatments of atherosclerosis among various relevant specialists. The conference was intended for practicing cardiologists, primary care physicians, medical geneticists, and physician–scientists. The conference included plenary sessions, specialty sessions, satellite symposia, an open competition for young scientists

Role of blood brain barrier failure in progression of cerebral small vessel disease: a detailed magnetic resonance imaging study

Small vessel disease (SVD) is an important cause of stroke, cognitive decline, and age-related disability. The cause of SVD is unknown, increasing evidence from neuropathology and neuroimaging suggests that failure of the blood-brain barrier (BBB) precipitates or worsens cerebral SVD progression and its failure is associated with SVD features such as white matter hyperintensities (WMH), perivascular spaces (PVS) and lacunar infarcts. The BBB change mechanism may also contribute to other common disorders of ageing such as Alzheimer's disease (AD). Magnetic resonance imaging (MRI) has revolutionised our understanding of SVD features. The MRI contributes to better understanding of the SVD pathophysiology and their clinical correlates. The purpose of this project was to better understand the pathogenesis of SVD, which involves improved understanding of BBB structures and pathophysiology and accurate measurement of cerebral SVD imaging characteristics on MRI scans. We aimed to assess (1) structures related to the BBB and factors that affect the BBB; (2) efficient and consistent WMH measurement method; (3) effect of stroke lesions on WMH and cerebral atrophy progression; (4) development and optimisation of computational PVS measurement method; (5) the relationships between PVS and SVD, blood markers, and BBB permeability. Section one describes structures and pathophysiology of the BBB. I reviewed the BBB structural and functional components from the view of neurovascular unit, PVS, and junctional proteins. The PVS part was done in a systematic search. I also reviewed some common stimuli for BBB permeability including inflammation and ischemia. Ischemic triggers for the BBB permeability were summarized systematically. Based on the literatures above, I summarized changes in junctional proteins in ischemia, inflammatory pain and AD models. Section two describes accurate measurement of WMH progression and atrophy. I used data from 100 patients who participated in a stroke study about BBB permeability changes in lacunar versus cortical stroke. To find a most efficient and consistent WMH measurement method, we tested several computational methods and effect of common processing steps including bias field correction and intensity adjustment. To avoid the effect of artefacts, I did a systematic search about artefacts and tested methods of image segmentation to avoid WMH artefacts as much as possible. To investigate the effect of stroke lesions on WMH and atrophy progression, I did the WMH, atrophy segmentation and stroke lesion measurements in a subgroup of 46 patients with follow-up scans, and showed that stroke lesions distorted measurement of WMH and atrophy progression and should be excluded. Section three describes development and optimization of a computational PVS measurement method, which measures the count and volume for PVS based on a threshold method using AnalyzeTM software. We tested the observer variability and validated it by comparison with visual rating scores. We investigated the associations between PVS results with other SVD features (WMH, atrophy), risk factors (hypertension, smoking and diabetes), blood markers, and BBB permeability. In conclusion, MRI is a valuable tool for the investigation of cerebral SVD features and BBB permeability. Exclusions of artefacts and stroke lesions are important in accurate measurement of WMH. PVS are important features of BBB abnormalities, and they correlate and share risk factors with other SVD features, and they should be considered as a marker of SVD and BBB permeability. Further systematic histological and ultrastructural studies of BBB are desirable in understanding the BBB regarding to the different parts of the cerebral vascular tree