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We evaluated the content of active form of TGF-β1 in the intact and post-infarction heart and the effect of this factor on the properties of epicardial cells. During the acute stage after myocardial infarction, the production of TGF-β1 in the heart increased, which closely correlated with activation of epicardial cells (appearance of a pool of Wt1+ epicardial cells entering the epithelial-mesenchymal transition). The role of TGF-β1 as the factor of epicardial activation was confirmed by the results of in vitro experiments: addition of recombinant TGF-β1 to cultured epicardial cells led to enhanced expression of genes of epithelial-mesenchymal transition and phenotypic transformation of these cells leading to the appearance of cells with markers of smooth muscle cells and fibroblasts. Our findings suggest that the regulatory axis “TGF-β1—epicardium cells” can be considered as an important link of the post-infarction reparative process and adaptive response during heart remodeling after myocardial infarction and as the target for therapeutic interventions.

Cells of all tissues in human body interact with their neighboring cells and components of the extracellular matrix thereby creating a unique 3D microenvironment. These interactions are realized through a complex network of biochemical and mechanical signals that are important in maintaining normal cellular homeostasis. Numerous attempts have been undertaken during the last two decades to develop 3D models for studying their properties and understanding the mechanisms of regulation of cell microenvironment in vivo. Cardiac spheroids (cardiospheres) are one these models of cardiac microenvironment. In this study we demonstrate that unique microenvironment formed in cardiospheres consists of stem/progenitor and mesenchymal cells surrounded by extracellular matrix proteins synthesized by these cells. TGF-β1 participates in the regulation of contraction of cells forming cardiospheres, promotes activation of the epithelial-mesenchymal transition and self-organization of cells, which leads to the formation of larger spheroids. Thereby, the effect of TGF-β1 on the cells of cardiospheres can serve as a model for studying the mechanisms of regulation of cardiac microenvironment.

Cognitive and behavioral factors are of great importance in the development of chronic insomnia, which explains the effectiveness of cognitive-behavioral therapy (CBT). CBT can be used both in combination with drug therapy and without it. This review gathers the existing information about conducting CBT, its various methods and effectiveness in comparison with drug therapy. CBT allows correcting erroneous thoughts (cognitive errors) and behavioral patterns that adversely affect the quality and duration of sleep. The issues of optimizing the use of CBT in clinical practice are discussed.

In heart attack, FSTL-1 is actively secreted by cardiomyocytes, accelerates growth of heart myofibrils and stimulates of vascular endothelial growth factor expression. The aim of this work was to investigate the effect of Etoxidol on synthesis of FSTL-1 in rats after myocardial infarction. The experiments were performed on Wistar rats weighing 250-350 g with simulated myocardial infarction or intact (group 5). Animals of control groups (groups 1, 2) were treated with saline for 7 and 14 days; Ethoxidol (24 mg/kg) was injected to animals of experimental groups (group 3, 4) (the daily dose was 6.36 mg/animal) for 6 or 14 days. The injection volume was 0.2 ml. At the beginning and at the end of the study plasma concentrations of FSTL-1 were determined by the ELISA method. Myocardial FSTL-1 gene expression was determined by real-time PCR. At the end of the experiments, the hearts were also used for histochemical analysis. To determine the size of the scar formed after the modeled heart attack, we used the classic Mallory staining method. The results show that the development of experimental acute myocardial infarction is accompanied by a significant increase in FSTL-1 expression in the heart, which was detected on the 7th day and stored increased by 14 days after a heart attack. After therapy with Ethoxidol, a tendency to a decrease in the expression of FSTL-1 by the 14th day was observed; it coincided with the dynamics of the plasma protein FSTL-1 level. It can be assumed that the downregulation trend in the FSTL-1 expression is associated with a more effective repair process after a heart attack, since FSTL-1 increases precisely in response to myocardial damage and decreases when the incentives for its expression from damaged heart tissue are reduced. Indirectly, this assumption is confirmed by the detected tendency to reduce the size of post-infarction fibrosis in the treatment with Ethoxidol. The results indicate the ability of Ethoxidol to influence FSTL-1 synthesis of in rats after myocardial infarction.Pri infarkte FSTL-1 aktivno sekretiruetsia kardiomitsitami, uskoriaet rost miofibrill serdtsa i stimuliruet ékspressiiu faktora rosta éndoteliia sosudov. Tsel' raboty zakliuchalas' v poiske lekarstvennogo sredstva, sposobnogo vliiat' na sintez FSTL-1 u krys posle infarkta miokarda. Opyty provedeny na krysakh linii Wistar massoĭ 250-350 g s modelirovannym infarktom miokarda i bez infarkta (gruppa 5). V techenie 7 i 14 dneĭ zhivotnym kontrol'nykh grupp (gruppy 1, 2) podkozhno vvodili fiziologicheskiĭ rastvor, a zhivotnym éksperimental'nykh grupp (gruppy 3, 4) vvodili étoksidol 1 raz v sutki v doze 24 mg/kg (sutochnaia doza sostavliala 6,36 mg/na zhivotnoe; sredniaia massa zhivotnogo — 265 g). Vvodimyĭ ob"em sostavlial 200 mkl, kontsentratsiia rastvora — 31,8 mg/ml. V den' operatsii preparat vvodili vnutrivenno, posleduiushchie 7 i 14 dneĭ — podkozhno. V nachale i v kontse issledovaniia kontsentratsiiu FSTL-1 v plazme krovi opredeliali metodom IFA. Ékspressiiu gena FSTL-1 opredeliali metodom PTsR. Po okonchanii opytov serdtsa ispol'zovali dlia gistokhimicheskogo analiza. Dlia opredeleniia razmerov sformirovavshegosia posle infarkta rubtsa ispol'zovali klassicheskiĭ metod okrashivaniia po Mallori. Poluchennye rezul'taty pokazyvaiut, chto razvitie ostrogo éksperimental'nogo infarkta miokarda soprovozhdaetsia znachitel'nym uvelicheniem ékspressii FSTL-1 v serdtse, kotoroe registriruetsia na 7 den' i sokhraniaetsia povyshennym na 14 den' posle infarkta. Posle terapii étoksidolom k 14 dniu otmechaetsia tendentsiia k snizheniiu ékspressii FSTL-1, chto sovpadaet s dinamikoĭ urovnia belka FSTL-1 v plazme krovi. Mozhno predpolozhit', chto tendentsiia k snizheniiu ékspressii FSTL-1 sviazana s bolee uspeshnym protsessom reparatsii posle infarkta, tak kak FSTL-1 povyshaetsia imenno v otvet na povrezhdenie miokarda i snizhaetsia, kogda stimuly k ego ékspressii iz povrezhdennoĭ tkani serdtsa umen'shaiutsia. Kosvenno éto predpolozhenie podtverzhdaetsia obnaruzhennoĭ tendentsieĭ k umen'sheniiu razmera postinfarktnogo fibroza pri lechenii étoksidolom. Poluchennye rezul'taty svidetel'stvuiut o sposobnosti étoksidola vliiat' na sintez FSTL-1 u krys posle infarkta miokarda.

It was suggested that the urokinase system plays a certain role in the regulation of activity of the endothelial-mesenchymal transition and in the development of perivascular fibrosis. Urokinase (uPA), the key component of the urokinase system, is a serine protease that binds to its receptor on the cell surface (uPAR) and affects the cell microenvironment components through the formation of plasmin, remodeling of the extracellular matrix, release of growth factors, and initiation of intracellular signals. The heart of PLAUR gene knockout C57BL/129 (uPAR-/-) mice showed signs of vasculopathy: reduced number of capillaries/arterioles, signs of endothelial-mesenchymal transition in endothelial cells, vascular wall remodeling, and deposition of extracellular matrix components. These changes were combined with enhanced expression of urokinase and active forms of TGF-β1. Apparently, uPAR is a part of a multicomponent system that provides multifaceted regulatory effects on the components of forming vessels and vascular wall cells, which allows considering it as a possible target for targeted antifibrotic therapy.

We studied the effect of 3D-culturing of cells in the form of cardiospheres on the expression of genes encoding vascular progenitor cell markers and angiogenesis regulators and on the production of proangiogenic factors. Cardiospheres were obtained by culturing mouse cardiac explants followed by self-assembly on poly-D-lysine. Gene expression was assessed by real-time PCR, and the production of proangiogenic factors was assessed by Microarray analysis of the cell secretome. It was found that cells in the cardiospheres in comparison with 2D-culture of cardiosphere-forming cells demonstrated increased expression of vascular progenitor cell markers (Pdgfrα, Kit, and Vegfr1) and angiogenesis regulatory factors (Vegf, Fgf2, and Angpt1), as well as an enhanced secretion of proangiogenic factors (ANGPT1, VEGF, CXCL16, and PIGF-2). Thus, culturing of cells in the form of cardiospheres can be considered as a basis for developing approaches to increasing their angiogenic activity and regenerative properties.

Vitronectin, extracellular matrix protein, plays an important role in embryonic development and in organ and tissue reparation. A unique characteristic of vitronectin is specific binding of various biological molecules, including urokinase receptor (uPAR), extracellular matrix components, adhesion receptors, growth factors, thus supporting the modulation of cell behavior. Vitronectin is in fact not found in intact myocardium, while after infarction its level increases significantly, which correlates with accumulation of uPAR+ progenitor cardiac cells in the focus. The cells isolated from the heart of wild type mice are characterized by higher adhesion to vitronectin than progenitor cardiac cells from the myocardium of uPAR knockout mice. In addition, inhibition of urokinase receptor with specific antibodies on the surface of the progenitor cardiac cells of wild type mice leads to attenuation of their adhesive activity and flattening on vitronectin matrix, which can be important for their distribution in the postinfarction myocardium and realization of the reparative functions.

We showed the possibility of generating combined tissue-engineered cell consisting of layers of rat cardiac stem cells and mesenchymal stromal cells from the adipose tissue. Cell-cell interaction within the cell sheet promoted proliferation of cardiac stem cells, expression of endothelial differentiation marker ETS1, and Notch signaling activation. The obtained results provide new insights into possible mechanisms of stimulation of endogenous regeneration processes after myocardial damage and demonstrate potential of cell-based cardiomyoplasty with the use of these combined cell sheets.

Mesenchymal stromal cells from rat adipose tissue were transduced with adeno-associated viral (AAV) vector encoding stem cell factor SCF that stimulates proliferation of cardiac c-kit+ cells and improved cardiac function and survival of animals after myocardial infarction. Extracellular vesicles isolated from the medium conditioned by mesenchymal stromal cells by ultracentrifugation were characterized by Western blotting, transmission electron microscopy, nanoparticle tracking analysis, immunostaining, and mass spectrometry analysis. Using proteomic analysis, we identified transgenic SCF in extracellular vesicles released by AAV-modified mesenchymal stromal cells and detected some proteins specific of extracellular vesicles secreted by transduced cells. Extracellular vesicles from AAV-transduced mesenchymal stromal cells could be used for delivery of transgenic proteins as they were readily endocytosed by both cardiosphere-derived cells and cardiac-progenitor cells.

We evaluated the content of active form of TGF-β1 in the intact and post-infarction heart and the effect of this factor on the properties of epicardial cells. During the acute stage after myocardial infarction, the production of TGF-β1 in the heart increased, which closely correlated with activation of epicardial cells (appearance of a pool of Wt1+ epicardial cells entering the epithelial-mesenchymal transition). The role of TGF-β1 as the factor of epicardial activation was confirmed by the results of in vitro experiments: addition of recombinant TGF-β1 to cultured epicardial cells led to enhanced expression of genes of epithelial-mesenchymal transition and phenotypic transformation of these cells leading to the appearance of cells with markers of smooth muscle cells and fibroblasts. Our findings suggest that the regulatory axis "TGF-β1-epicardium cells" can be considered as an important link of the post-infarction reparative process and adaptive response during heart remodeling after myocardial infarction and as the target for therapeutic interventions.

Now, great interest is connected with application of the cells received directly from a myocardium as the tool for stimulation of angiogenesis and reparative processes in heart. The aim of the present research is studying of angiogenic properties in vitro and in vivo of c-kit+-cells, obtained from hearts of small rodents. The work was performed on male C57BL/6 mice and male Wistar rats. The study used methods of cytofluorimetry, immuno-fluorescent staining, models of myocardial infarction and subcutaneous angiogenesis in Matrigel™. It was shown, that after acute myocardial infarction c-kit+ cells activated, part of which entered into endothelial differentiation and integrated into de novo formed vessels. C-kit+-expressed the markers of vascular progenitor cells, exhibited endothelial-like behavior in vitro, and after subcutaneous transplantation increased vascularization of Matrigel™. This is achieved both due to the paracrine effects, which stimulate the growth of the recipient's mouse vessels into the Matrigel implant, and partially due to the differentiation of the transplanted cells into the vascular endothelium cells, which was confirmed by vital dye staining. Thus, c-kit+-cells derived from the myocardium can be considered as a promising type of resident cells exhibiting the properties of progenitor cells of the heart vessels for developing approaches to stimulate vascularization of the ischemic myocardium.

We studied the effect of SIRT1 deacetylase and PPARγ receptor activators on proinflammatory (M1), anti-inflammatory (M2) polarization of RAW264.7 macrophages and their modulating effects on insulin sensitivity of adipocytes. In M1 macrophages, the expression of TNFα and CXCL9, secretion of CXCL11, ROS generation, and content of dendritic-like cells were elevated. In M2 macrophages, expression of IGF-1 and ALOX15 factors was enhanced. SIRT1 activator (DCHC) and PPARγ receptor ligand (rosiglitazone) reduced expression of inflammatory markers TNFα and CXCL9 and increased expression of IGF-1 and ALOX15. SIRT1 inhibitor Ex527 increased the proportion of dendritic cells in macrophage populations. The paracrine effect of M1-macrophage-conditioned media attenuated insulin-dependent phosphorylation of threonine (Thr308) in Akt kinase and enhanced phosphorylation of serine (Ser473). This effect was attenuated by DCHC and rosiglitazone.

This literature review deals with knowledge and beliefs about epilepsy and with the attitude of patients, relatives, and society as a whole towards epilepsy. It discusses the stigma that is associated with the disease and has a strong impact on patients with epilepsy and their families. The problems of stigma or related concepts in different countries are analyzed.

Resident cardiac progenitor cells reside in the adult heart and govern myocardial homeostasis and repair after injury. Many experimental and clinical studies are being completed with encouraging results. However, the mechanisms of the therapeutic action of CPC remain poorly understood. Initially they were explained by the ability of CPC to differentiate into cardiomyocytes and vascular cells, recently their regenerative effects are mainly explained by secretion biologically active molecules and the release of exosomes, which promote activation of the regenerative program in the heart cells. The aim of the present study is to assess the effect of intramyocardial CPC transplantation on the activation of the vasculogenic pool of epicardial cells. In our study we ligated the anterior descending coronary artery in the hearts of male Wistar rats and intramyocardial injections of a fluorescently labeled (CM-DIL+) CPC or control medium were performed. Fourteen days after transplantation, CPC retained viability, proliferation properties and some cells showed signs of vasculogenic differentiation. We did not find significant differences in the infarct size between two groups assessed by morphometric studies. However, CPC transplantation attenuated adverse remodeling: we found reduction in left ventricular dilatation, severity of transmural injury and activation of arteriogenesis in the border zone. By immunofluorescence staining of myocardial sections, obtained after CPC transplantation, we found a significant increase the number of Wt1+ cells in the epicardium, indicating activation of the epithelial-mesenchymal transition and the formation of epicardial progenitor cells (EPC). EPC migrated to the myocardium, some of them coexpressed markers CD31 (Pecam), alpha-smooth muscle actin (a-SMA), and participated in the new vessels formation. Thus, intramyocardial CPC transplantation increased the vascularization of the myocardium by differentiation of the transplanted cells, as well as the activation of vasculogenic epicardial cells, which can contribute the reduction of negative cardiac remodeling.

A new trend in modern experimental cardiology is the development of approaches to correction of reparation after myocardial infarction (MI) with the use of specific effects on immune cells. One of the main targets for such interventions is the process of macrophage's polarization in the infarction zone. Proinflammatory M1‑macrophages contribute to hampered myocardial repair, in contrast to M2‑macrophages that promote regeneration. Currently, there are two main ways of targeted delivery of agents necessary for macrophage reprogramming - inlipoid and inglycan-encapsulated particles. As modulating agents, small interfering RNA and other genetic constructions are usually used. Both these approaches are currently awaiting their translation into cardiology. The most physiological approach to reprogramming of immune cells may consist in attempts to switch the metabolism of the immune cell from glycolytic to oxidative, which allows macrophages to switch from M1 to M2 phenotype. Among possible targets for macrophage reprogramming, it is worthwhile to isolate the protein complex mTORC1, the blocking of which promotes oxidative metabolism, and the transcription factor HIF-1α, the blocking of which also facilitates the switching of the metabolism from glycolytic to oxidative one.

Proliferation, subsequent migration to the damaged area, differentiation into appropriate cell types, and/or secretion of biologically active molecules and extracellular vesicles are important processes that underlie the involvement of stem/progenitor cells in the repair and regeneration of tissues and organs. All these functions are regulated through the interaction between stem cells and the microenvironment in the tissue cell niches that control these processes through direct cell-cell interactions, production of the extracellular matrix, release of extracellular vesicles, and secretion of growth factors, cytokines, chemokines, and proteases. One of the most important proteolytic systems involved in the regulation of cell migration and proliferation is the urokinase system represented by the urokinase plasminogen activator (uPA, urokinase), its receptor (uPAR), and inhibitors. This review addresses the issues of urokinase system involvement in the regulation of stem cell niches in various tissues and analyzes the possible effects of this system on the signaling pathways responsible for the proliferation, programmed cell death, phenotype modulation, and migration properties of stem cells.

We studied the effect of urokinase, its recombinant forms, and domain fragments on migration and proliferation of adipose tissue mesenchymal stromal cells (MSCs) and MMP secretion by these cells. Urokinase, but not its recombinant forms, slightly induced directed migration of MSCs. Spontaneous migration of MSCs increased under the action of urokinase or its isolated kringle domain. Migration induced by platelet-derived growth factor was inhibited by proteolytically inactive form of urokinase, the kringle domain, and blocking antibody to urokinase receptor. Urokinase, its proteolytically inactive form, and kringle domain produced no effect on MSC proliferation. In contrast to platelet-derived growth factor, all urokinase forms induced secretion of MMP-9 by MSCs.

The article considers the problem of social restrictions caused by epilepsy. Information on historical aspects and discrimination of patients with epilepsy is presented. The authors consider factors influencing marital status of patients in different countries and present information on the differences in medical restrictions to driving in different countries and in the Russian Federation. Employment status of patients with epilepsy, restrictions related to objective reasons and attitudes of patients and others toward epilepsy are elucidated.В статье рассматривается проблема социальных ограничений, связанных с заболеванием эпилепсией. Приведены данные об исторических аспектах заболевания и дискриминации в отношении пациентов с эпилепсией. Рассмотрены факторы, влияющие на семейное положение пациентов в разных странах. Представлена информация о различиях системы ограничения управления транспортом для пациентов с эпилепсией в различных странах мира и в Российской Федерации. Освещены особенности трудоустройства больных эпилепсией, ограничения, связанные с объективными причинами и представлениями окружающих и самих пациентов о своем заболевании.

A stimulating effect of a combination of hepatocyte growth factor (HGF) and glial neurotrophic factor (GDNF) on the growth of neurites in the spinal ganglion model was demonstrated. The mechanism of neurite growth in the spinal ganglion model is associated with transactivation of HGF c-met receptor in the presence of both HGF and GDNF. The combination of HGF and GDNF significantly activated mitogenic signaling cascade mediated by protein kinases ERK1/2, which can be a mechanism for increasing the number of neurites. Our findings can be used for developing effective methods for restoring impaired peripheral nerve function after traumatic and ischemic injury using a combination of GDNF and HGF.

A new trend in modern experimental cardiology is the development of approaches to correction of reparation after myocardial infarction (MI) with the use of specific effects on immune cells. One of the main targets for such interventions is the process of macrophage's polarization in the infarction zone. Proinflammatory M1‑macrophages contribute to hampered myocardial repair, in contrast to M2‑macrophages that promote regeneration. Currently, there are two main ways of targeted delivery of agents necessary for macrophage reprogramming - inlipoid and inglycan-encapsulated particles. As modulating agents, small interfering RNA and other genetic constructions are usually used. Both these approaches are currently awaiting their translation into cardiology. The most physiological approach to reprogramming of immune cells may consist in attempts to switch the metabolism of the immune cell from glycolytic to oxidative, which allows macrophages to switch from M1 to M2 phenotype. Among possible targets for macrophage reprogramming, it is worthwhile to isolate the protein complex mTORC1, the blocking of which promotes oxidative metabolism, and the transcription factor HIF-1α, the blocking of which also facilitates the switching of the metabolism from glycolytic to oxidative one.

Proteolytically inactive recombinant forms of urokinase (uPAHQ and amino-terminal fragment) inhibit spontaneous migration of endothelial cells; amino-terminal fragment also suppresses angiogenesis stimulated by basic fi broblast growth factor in vitro. These fi ndings suggest the possibility of using synthesized proteolytically inactive recombinant forms of urokinase for the regulation of endothelial cell migration and suppression of neoangiogenesis.

To assess the psychometric properties of the Stigma Scale of Epilepsy, a short simple to complete questionnaire to quickly and reliably determine the presence and the level of perceived stigma in a particular patient, as well as to assess the prevalence, socio-demographic, clinical and socio-psychological factors associated with this phenomenon.The study included 398 patients with epilepsy. Exploratory (EFA) and confirmatory factor analysis (CFA) were used to assess the psychometric characteristics of the scale.The EFA showed a two-factor scale structure explaining 57.25% of the variance. Values of GFI 0.948, CFI 0.927 and RMSEA 0.057 after the data correction show a good conformity of the model to the empirical data. Cronbach's alpha coefficient was 0.862 for the scale, 0.815 for factor 1, 0.809 for factor 2, which indicates a high consistency of both the entire scale and its subscales. The Russian-language variant of the Stigma Scale of Epilepsy is a short, economical to use tool with good psychometric properties for assessing perceived stigma in patients with epilepsy.Цель исследования. Изучение психометрических свойств шкалы стигмы при эпилепсии - короткого, удобного для заполнения инструмента, который позволяет быстро и достоверно определить наличие и уровень стигмации у конкретного пациента, а также оценить распространенность, социально-демографические, клинические и социально-психологические факторы, связанные с этим феноменом. Материал и методы. Обследовали 398 больных эпилепсией. Все прошли тестирование по шкале стигмы. Для оценки шкалы использовались эксплораторный (ЭФА) и конфирматорный факторный анализ (КФА). Результаты и заключение. ЭФА показал двухфакторную структуру шкалы, объясняющую 57,25% дисперсии данных. Показатели GFI - 0,948, CFI - 0,927 и RMSEA - 0,057 после произведенной коррекции свидетельствовали о хорошем соответствии модели эмпирическим данным. Значение коэффициента α Кронбаха для шкалы составило 0,862, для фактора 1 - 0,815, для фактора 2 - 0,809, что выявило высокую согласованность как всей шкалы, так и ее субшкал. Таким образом, русскоязычный вариант шкалы стигмы при эпилепсии является кратким, экономичным в использовании, с хорошими психометрическими свойствами инструментом для оценки воспринимаемой стигмы у больных эпилепсией.

AIM: To evaluate the plasma level of circulating heptocyte growth factor (HGF) in patients with comorbidity of post-infarction chronic heart failure (CHF), type 2 diabetes mellitus (T2DM) and obesity. We also aimed to assess possible correlations between HGF levels and parameters of carbohydrate and lipid metabolism, as well as myocardial functional characteristics and classic biochemical severity markers for CHF.17Сахар ный диабет КардиологияСахарный диабет. 2013;(2):17-25 MATERIALS AND METHODS: We enrolled 100 patients for participation in this study, including the following subgroups: 20 individuals with- out cardiovascular and glycemic disorders, 30 patients with CHF, 25 patients with CHF/T2DM comorbidity and 25 diabetic patients with no signs of heart failure. Quantitative plasma HGF analysis was performed with enzyme-linked immunosorbent assay (ELISA). RESULTS: Plasma HGF was elevated both in patients with CHF and T2DM as measured against healthy control group. The elevation was most prominent in patients with CHF/T2DM comorbidity and was found to correlate with HbA1c level (r=0.52, p=0.03). Plasma HGF also correlated with BMI (r=0.42, p=0007) in a unified study group, though we observed no statistically significant difference between subgroups with a trend toward higher HGF in obese patients with CHF/T2DM comorbidity (626.1?254.1 pg/ml vs 742.0?210.7 pg/ml respectively; p 0.05). Interestingly, plasma HGF was also significantly higher in controls with BMI 30 km/m2 (324.1?107.7 pg/ml vs 436.9?112.3 pg/ml, p=0.03).Circulating HGF correlated with plasma levels of N-terminal fragment of B-type natriuretic peptide (NT-proBNP) and such structural and functional myocardial characteristics as left atrial size and maximum volume along with left ventricular ejection fraction (EF), end-diastolic volume (EDV) and end-diastolic dimension (EDD). CONCLUSION: These findings suggest that HGF may potentially serve as a prediction marker for unfavorable myocardial remodeling and poor prognosis in CHF patients with T2DM and obesity, though this possibility should be further investigated in follow-up studies.

Arterial remodeling is the process of adaptation of the vessel comprising multiple structural and functional alterations of the vascular wall that occur in disease, trauma or aging. Arterial remodeling is accelerated in conditions that adversely affect the structural and functional balance of the vascular system, such as hypertension, atherosclerosis, kidney disease, inflammatory diseases, genetic abnormalities, and mechanical damage. Pathological changes in the vascular wall lead to organ damage and, ultimately, death. The aim of this paper is to review the various factors and complex mechanisms, which underlie negative arterial remodeling after mechanical injury and data indicating on the key role of the urokinase plasminogen activator in this process.

Aim. To study effect of concomitant type 2 diabetes mellitus on the number of circulating progenitor cells (CPC) in patients with coronary heart disease(CHD) and postinfarction heart failure (ischemic cardiomyopathy). Methods. The number of CPC (CD34+ cells) was determined by flow cytophotometry in 47 patients with CHD including 14 with CHD + DM2; 12patients without CHD and DM2 made up the control grouP. Enzyme-linked immunosorbent assay was used to measure N-terminal precursor of brainnatriuretic peptide (NT-proBNP), immunoreactive insulin (IRI) and C-peptide levels. Results. The number of CPC in patients with ischemic cardiomyopathy without DM2 was 33.4% greater than in controls. In patients with cardiomyopathyand DM2 the number of CPC depended on the quality of diabetes compensation. It was lowest in case of decompensated DM2 (HbA 1c =9.5?1.8%).In patients with compensated/subcompensated DM2 (HbA 1c =6.8?0.3%) it was significantly higher than in controls and patients with ischemiccardiomyopathy without DM2 (mean 46.5 (p=0.006) and 40.0% (p=0.02) respectively). Conclusion. The number of CPC in peripheral blood of patients with ischemic cardiomyopathy and DM2 correlated with the level of DM compensation.It was lowest in patients with decompensated DM2 and exceeded the normal number in patients with CHD without DM2. The number of CPC inverselycorrelated with blood glucose level. Positive correlation of CPC number with IRI and C-peptide levels was documented in control subjects and patientswith CHD without DM2.

Adipose issue is a source of mesenchymal stem cells (MSC) that can be used to stimulate blood vessel growth in ischemic tissues. Various metabolicdisorders including hypeglycemia may have negative effect on therapeutic properties of these cells. Aim. To study the influence of high glucose concentration on functional activity in human adipose tissue. Materials and methods. Flow cytometry and real time PCR were used to study functional activity of cultured MSC from human adipose issue at highglucose concentration. Results. Prolonged (10-12 days) incubation at a high glucose concentration (25 mM) suppressed the ability of MSC to stimulate angiogenesis. Also,glucose modified expression of genes activating and inhibiting angiogenesis but had no effect on MSC proliferation and apoptosis. Conclusion. High glucose concentration suppresses angiogenic activity of MSC in adipose tissue; it may account for incomplete restoration of bloodflow in diabetic patients.

In the past few years, it has been established that the heart contains a reservoir of stem and progenitor cells. These cells are able to differentiate in cardiomyogenic, endothelial, and smooth muscle lineages in vitro and in vivo and, following injection into an infarcted myocardium, these cells prevent the remodeling of the left ventricle and improve cardiac function. The aim of the present study was the immunophenotypic characterization of resident stem cells in the tissue of a chronic left aneurism, an analysis of their localization, and distribution in various aneurism areas. Fifteen samples of aneurism tissue obtained surgically were analyzed. The number of cells positive for c-kit stem-cell marker was about 3327 ± 234 cells per 1 cm3 tissue. Single cells were found in fibrous, muscle, and adipose parts of aneurism tissue. Most of the cells were revealed in fibrous tissue near large vessels; however, the coexpression of c-kit and markers of endothelial cells was not observed. C-kit-positive cells did not express CD34 and CD45 markers and, thereby, were not of hematopoietic origin. The majority of c-kit-positive cells expressed MDR1, another stem-cell marker. These c-kit-positive cells did not proliferate, since they did not express Ki67. About 20% of these cells expressed an inhibitor of cyclin-dependent kinase p21cip/Waf1. C-kit cells did not express markers of cardiomyocytes (Nkx 2.5, Gata 4, Mef2c, α-actinin), endothelium (Ets 1, CD105, wW), and smooth muscle cells (Gata 6, SMA). Single-cell clusters made up of 70–100 c-kit-positive cells (in cell niches) were observed; however, no markers of cardiomyogenic differentiation were expressed in these cells. Thus, aneurism tissue of the left ventricle contains c-kit-positive cells that, are most likely resident cardiac stem cells; however, their regenerative capacity should be further explored.