ПРОДУКЦИЯ ФАКТОРОВ РОСТА И ДЕСКВАМАЦИЯ ЭНДОТЕЛИОЦИТОВ В СЕРДЦЕ ПРИ ИШЕМИЧЕСКОЙ КАРДИОМИОПАТИИ

oai:oai.kpccz.elpub.ru:article/1324Highlights Dysregulation of angiogenesis may be the pathogenetic factor of ischemic cardiomyopathy (ICMP). Aim. To determine the content of growth factors and desquamated endothelial cells (DEC) in the blood from the coronary sinus and ulnar vein in association with the number of progenitor endothelial cells (PEC) in the blood from the ulnar vein in patients with coronary heart disease (CHD), suffering and not suffering from ICMP.Methods. The study included 30 patients with ICMР and 22 patients with CHD, and 18 healthy donors. The content of DEC (CD45–CD146+) was determined in blood from the cubital vein (peripheral) and coronary sinus, and the content of DEC (CD14+CD34+VEGFR2+) was determined in peripheral blood by flow cytometry (antibodies “BD Biosciences”, USA). The concentrations of VEGF-A, VEGF-B, PDGF, SDF-1, SCF, FGF-1, TGF-β1 in blood plasma from both locations were evaluated by multiplex analysis (set “Cloud-Clone Corp.”, USA).Results. The content of DEC in peripheral blood was elevated in patients with CHD of both groups, and in patients with ICMP in sinus blood was higher than in peripheral. At the same time, in patients with CHD without cardiomyopathy, an excess of PEC and SDF-1 in the blood from the ulnar vein was established in combination with an increase in the concentration of PDGF and a decrease in the content of VEGF-B in the blood from the coronary sinus relative to the parameters of systemic blood flow. In patients with ICMP, these changes were not detected, but there was an increase in the concentration of TGF-β1 in sinus blood compared with peripheral blood. Regardless of the presence of ICMP, the concentration of SCF, FGF-1, VEGF-A in the blood from the ulnar vein corresponded to the norm and that in sinus blood; the content of VEGF-A in the coronary bloodstream exceeded its systemic level.Conclusion. In patients with ICMP, desquamation of the coronary vascular endothelium is enhanced against the background of violations of its repair processes due to insufficient (relative to CHD without cardiomyopathy) mobilization of PEC from the bone marrow due to the absence of an excess of SDF-1 in the blood and their insufficient homing into the myocardium due to weak PDGF production in the heart.Основные положенияПатогенетическим фактором ишемической кардиомиопатии может быть нарушение регуляции ангиогенеза. Цель. Определить содержание факторов роста и десквамированных эндотелиальных клеток (ДЭК) в крови из коронарного синуса и локтевой вены в ассоциации с численностью прогениторных эндотелиальных клеток (ПЭК) в крови из локтевой вены у больных ишемической болезнью сердца (ИБС), страдающих и не страдающих ишемической кардиомиопатией (ИКМП).Материалы и методы. В исследование включили 30 пациентов с ИБС и ИКМП, 22 больных ИБС без ИКМП, 18 здоровых доноров. Содержание ДЭК (CD45–CD146+) определяли в крови из локтевой вены (периферическая) и коронарного синуса (синусовая), а содержание ПЭК (CD14+CD34+VEGFR2+) – в периферической крови методом проточной цитофлуориметрии (антитела BD Biosciences, США). В плазме обоих образцов крови оценивали концентрацию VEGF-A, VEGF-B, PDGF, SDF-1, SCF, FGF-1, TGF-β1 методом мультиплексного анализа (набор Cloud-Clone Corp., США).Результаты. Содержание ДЭК в периферической крови было повышенным у больных ИБС обеих групп, а в синусовой крови у пациентов с ИКМП было выше, чем в периферической. У больных ИБС без ИКМП установлен избыток ПЭК и SDF-1 в крови из локтевой вены в сочетании с увеличением концентрации PDGF и снижением содержания VEGF-В в крови из коронарного синуса относительно параметров системного кровотока. У пациентов с ИКМП данные изменения не выявлены, но отмечен рост концентрации TGF-β1 в синусовой крови по сравнению с периферической. Вне зависимости от ИКМП концентрация SCF, FGF-1, VEGF-А в крови из локтевой вены соответствовала норме и таковой в синусовой крови; содержание VEGF-А в коронарном кровотоке превышало системный уровень.Заключение. При ИКМП усилена десквамация эндотелия коронарных сосудов на фоне нарушений его репарации за счет недостаточной (относительно ИБС без ИКМП) мобилизации ПЭК из костного мозга ввиду отсутствия избытка SDF-1 в крови и недостаточного их хоминга в миокард вследствие слабой продукции PDGF в сердце

Endothelial Function and Hypoxic–Hyperoxic Preconditioning in Coronary Surgery with a Cardiopulmonary Bypass: Randomized Clinical Trial

A hypoxic–hyperoxic preconditioning (HHP) may be associated with cardioprotection by reducing endothelial damage and a beneficial effect on postoperative outcome in patients undergoing cardiac surgery with cardiopulmonary bypass (CPB). Patients (n = 120) were randomly assigned to an HHP and a control group. A safe, inhaled oxygen fraction for the hypoxic preconditioning phase (10–14% oxygen for 10 min) was determined by measuring the anaerobic threshold. At the hyperoxic phase, a 75–80% oxygen fraction was used for 30 min. The cumulative frequency of postoperative complications was 14 (23.3%) in the HHP vs. 23 (41.1%), p = 0.041. The nitrate decreased after surgery by up to 20% in the HHP group and up to 38% in the control group. Endothelin-1 and nitric oxide metabolites were stable in HHP but remained low for more than 24 h in the control group. The endothelial damage markers appeared to be predictors of postoperative complications. The HHP with individual parameters based on the anaerobic threshold is a safe procedure, and it can reduce the frequency of postoperative complications. The endothelial damage markers appeared to be predictors of postoperative complications

The phylodynamics of the rabies virus in the Russian Federation

<div><p>Near complete rabies virus N gene sequences (1,110 nt) were determined for 82 isolates obtained from different regions of Russia between 2008 and 2016. These sequences were analyzed together with 108 representative GenBank sequences from 1977–2016 using the Bayesian coalescent approach. The timing of the major evolutionary events was estimated. Most of the isolates represented the steppe rabies virus group C, which was found over a vast geographic region from Central Russia to Mongolia and split into three groups (C0-C2) with discrete geographic prevalence. A single strain of the steppe rabies virus lineage was isolated in the far eastern part of Russia (Primorsky Krai), likely as a result of a recent anthropogenic introduction. For the first time the polar rabies virus group A2, previously reported in Alaska, was described in the northern part of European Russia and at the Franz Josef Land. Phylogenetic analysis suggested that all currently circulating rabies virus groups in the Russian Federation were introduced within the few last centuries, with most of the groups spreading in the 20^th century. The dating of evolutionary events was highly concordant with the historical epidemiological data.</p></div

Automated Solid-Phase Click Synthesis of Oligonucleotide Conjugates: From Small Molecules to Diverse <i>N</i>‑Acetylgalactosamine Clusters

We developed a novel technique for the efficient conjugation of oligonucleotides with various alkyl azides such as fluorescent dyes, biotin, cholesterol, <i>N</i>-acetylgalactosamine (GalNAc), etc. using copper-catalysed alkyne–azide cycloaddition on the solid phase and CuI·P­(OEt)₃ as a catalyst. Conjugation is carried out in an oligonucleotide synthesizer in fully automated mode and is coupled to oligonucleotide synthesis and on-column deprotection. We also suggest a set of reagents for the construction of diverse conjugates. The sequential double-click procedure using a pentaerythritol-derived tetraazide followed by the addition of a GalNAc or Tris–GalNAc alkyne gives oligonucleotide–GalNAc dendrimer conjugates in good yields with minimal excess of sophisticated alkyne reagents. The approach is suitable for high-throughput synthesis of oligonucleotide conjugates ranging from fluorescent DNA probes to various multi-GalNAc derivatives of 2′-modified siRNA

Diversities in the Gut Microbial Patterns in Patients with Atherosclerotic Cardiovascular Diseases and Certain Heart Failure Phenotypes

To continue progress in the treatment of cardiovascular disease, there is a need to improve the overall understanding of the processes that contribute to the pathogenesis of cardiovascular disease (CVD). Exploring the role of gut microbiota in various heart diseases is a topic of great interest since it is not so easy to find such reliable connections despite the fact that microbiota undoubtedly affect all body systems. The present study was conducted to investigate the composition of gut microbiota in patients with atherosclerotic cardiovascular disease (ASCVD) and heart failure syndromes with reduced ejection fraction (HFrEF) and HF with preserved EF (HFpEF), and to compare these results with the microbiota of individuals without those diseases (control group). Fecal microbiota were evaluated by three methods: living organisms were determined using bacterial cultures, total DNA taxonomic composition was estimated by next generation sequencing (NGS) of 16S rRNA gene (V3&ndash;V4) and quantitative assessment of several taxa was performed using qPCR (quantitative polymerase chain reaction). Regarding the bacterial culture method, all disease groups demonstrated a decrease in abundance of Enterococcus faecium and Enterococcus faecalis in comparison to the control group. The HFrEF group was characterized by an increased abundance of Streptococcus sanguinus and Streptococcus parasanguinis. NGS analysis was conducted at the family level. No significant differences between patient&rsquo;s groups were observed in alpha-diversity indices (Shannon, Faith, Pielou, Chao1, Simpson, and Strong) with the exception of the Faith index for the HFrEF and control groups. Erysipelotrichaceae were significantly increased in all three groups; Streptococcaceae and Lactobacillaceae were significantly increased in ASCVD and HFrEF groups. These observations were indirectly confirmed with the culture method: two species of Streptococcus were significantly increased in the HFrEF group and Lactobacillus plantarum was significantly increased in the ASCVD group. The latter observation was also confirmed with qPCR of Lactobacillus sp. Acidaminococcaceae and Odoribacteraceae were significantly decreased in the ASCVD and HFrEF groups. Participants from the HFpEF group showed the least difference compared to the control group in all three study methods. The patterns found expand the knowledge base on possible correlations of gut microbiota with cardiovascular diseases. The similarities and differences in conclusions obtained by the three methods of this study demonstrate the need for a comprehensive approach to the analysis of microbiota